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Quick Reference
  • Normal Range: 80-100 mmHg (breathing room air at sea level)
  • Age-Adjusted Normal: PaO2 = 104 - (0.27 × age in years)
  • Critical Hypoxemia: PaO2 <60 mmHg (requires supplemental oxygen)
  • Severe Hypoxemia: PaO2 <40 mmHg (life-threatening)
  • Primary Use: Assess oxygenation adequacy, diagnose hypoxemia, guide oxygen therapy
  • Sample Type: Arterial blood (radial, femoral, or brachial artery)
  • Key Point: Must interpret with FiO2 (inspired oxygen) - use P/F ratio for ARDS classification

Test Description

What is PaO2?

PaO2 (Partial Pressure of Oxygen in arterial blood) measures the amount of oxygen dissolved in arterial blood plasma. It reflects the effectiveness of gas exchange in the lungs and is the primary indicator of oxygenation status.

Physiological Role

PaO2 is determined by the efficiency of oxygen transfer from alveoli to pulmonary capillary blood:

  • Alveolar oxygen (PAO2): Oxygen present in alveolar air available for diffusion
  • Diffusion across alveolar-capillary membrane: Oxygen moves down concentration gradient from alveoli to blood
  • Arterial oxygen (PaO2): Oxygen dissolved in plasma after gas exchange
  • Oxygen-hemoglobin binding: PaO2 drives oxygen binding to hemoglobin (measured as SaO2)

Clinical Importance

PaO2 is essential for assessing respiratory and cardiovascular function:

  • Hypoxemia detection: Identifies inadequate oxygenation requiring intervention
  • Respiratory failure classification: Type I (hypoxemic) vs Type II (hypercapnic) respiratory failure
  • Oxygen therapy guidance: Determines need for supplemental oxygen and target FiO2
  • Mechanical ventilation: Guides PEEP and FiO2 settings to optimize oxygenation
  • ARDS diagnosis: P/F ratio (PaO2/FiO2) defines and classifies acute respiratory distress syndrome
PaO2 vs SaO2

PaO2 measures oxygen dissolved in plasma, while SaO2 measures percentage of hemoglobin saturated with oxygen. Due to the sigmoid oxygen-hemoglobin dissociation curve, SaO2 remains >90% until PaO2 drops below 60 mmHg. PaO2 is more sensitive for detecting early hypoxemia, while SaO2 reflects oxygen delivery capacity.

Normal Ranges

PaO2 normal ranges vary with age, altitude, and inspired oxygen concentration (FiO2). Values listed are for sea level breathing room air (FiO2 21%).

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Population PaO2 Range (mmHg) Notes
Young Adults (<30 years) 95-100 Peak lung function
Adults (30-60 years) 80-100 Standard reference range
Elderly (>60 years) Use age-adjusted formula PaO2 = 104 - (0.27 × age)
Age 70 85 (predicted) 104 - (0.27 × 70) = 85 mmHg
Age 80 82 (predicted) 104 - (0.27 × 80) = 82 mmHg
Age-Adjusted Normal

PaO2 decreases approximately 0.27 mmHg per year due to age-related changes in lung compliance, alveolar surface area, and V/Q matching. Use the formula PaO2 = 104 - (0.27 × age) to calculate expected PaO2 for elderly patients. For example, a PaO2 of 70 mmHg is abnormal in a 30-year-old but normal for an 80-year-old.

Important Considerations
  • Altitude adjustment: PaO2 decreases at high altitude due to lower atmospheric pressure; normal range is lower in Denver (elevation 5,280 ft) vs sea level
  • FiO2 dependency: PaO2 increases with supplemental oxygen; always interpret PaO2 in context of FiO2 (use P/F ratio for standardization)
  • Position effects: PaO2 may be 5-10 mmHg lower when supine vs upright due to basilar atelectasis
  • Sample handling: PaO2 decreases if sample sits at room temperature due to cellular oxygen consumption; analyze within 30 minutes or place on ice
Clinical Significance

Hypoxemia Classification

Hypoxemia severity guides urgency of intervention and oxygen therapy:

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Classification PaO2 Range (mmHg) Clinical Significance
Normal 80-100 Adequate oxygenation
Mild Hypoxemia 60-79 Compensated; monitor closely; consider supplemental O2
Moderate Hypoxemia 40-59 Significant impairment; supplemental O2 required
Severe Hypoxemia <40 Life-threatening; urgent intervention; consider intubation
Critical Threshold - PaO2 <60 mmHg

This is the inflection point on the oxygen-hemoglobin dissociation curve where SaO2 drops precipitously. Below 60 mmHg, small decreases in PaO2 cause large drops in SaO2 and oxygen delivery. PaO2 <60 mmHg is an absolute indication for supplemental oxygen therapy.

Five Causes of Hypoxemia

Understanding the mechanism of hypoxemia guides diagnostic workup and treatment:

1. Ventilation-Perfusion (V/Q) Mismatch

  • Mechanism: Alveolar ventilation does not match perfusion; low V/Q units (perfusion exceeds ventilation)
  • A-a gradient: Elevated (widened)
  • Response to O2: Corrects with supplemental oxygen
  • Common causes: Pneumonia, pulmonary embolism, atelectasis, COPD, asthma, pulmonary edema
  • Most common cause: Accounts for majority of hypoxemia in clinical practice

2. Shunt (Intrapulmonary or Cardiac)

  • Mechanism: Blood bypasses alveolar gas exchange (extreme V/Q mismatch with V/Q = 0)
  • A-a gradient: Severely elevated
  • Response to O2: Minimal or no improvement with 100% oxygen (hallmark of shunt)
  • Intrapulmonary shunt causes: Severe pneumonia, ARDS, pulmonary edema, pulmonary AVM
  • Cardiac shunt causes: Right-to-left cardiac shunt (Eisenmenger syndrome, ASD/VSD/PDA with reversal)
  • Calculation: Shunt fraction >30% causes refractory hypoxemia

3. Hypoventilation

  • Mechanism: Reduced alveolar ventilation decreases alveolar oxygen (PAO2)
  • A-a gradient: Normal (key differentiating feature)
  • Response to O2: Corrects easily with supplemental oxygen
  • ABG pattern: Hypoxemia + hypercapnia (elevated PaCO2)
  • Common causes: Opioid overdose, neuromuscular disease, obesity hypoventilation, severe COPD exacerbation, central sleep apnea
  • Mechanism recognition: Only cause with normal A-a gradient and elevated PaCO2

4. Diffusion Impairment

  • Mechanism: Thickened alveolar-capillary membrane impairs oxygen diffusion
  • A-a gradient: Elevated (worsens with exercise)
  • Response to O2: Corrects with supplemental oxygen
  • Common causes: Interstitial lung disease (pulmonary fibrosis), pulmonary edema, ARDS
  • Exercise characteristic: Hypoxemia worsens with exertion due to reduced capillary transit time
  • Rare isolated cause: Usually combined with V/Q mismatch in clinical practice

5. Low Inspired Oxygen (Low FiO2)

  • Mechanism: Decreased atmospheric PO2 reduces alveolar oxygen
  • A-a gradient: Normal
  • Response to O2: Corrects with supplemental oxygen
  • Common causes: High altitude, enclosed space fire (oxygen consumption), incorrect ventilator FiO2 setting
  • High altitude: PaO2 ~60 mmHg at 10,000 feet; triggers hyperventilation and respiratory alkalosis
Mnemonic - "Five Causes of Hypoxemia" (VSHD-L)
  • V = V/Q mismatch (most common)
  • S = Shunt (refractory to O2)
  • H = Hypoventilation (normal A-a gradient + high CO2)
  • D = Diffusion impairment (worsens with exercise)
  • L = Low inspired O2 (altitude, fire)
Interpretation Guidelines

Alveolar-Arterial (A-a) Gradient

The A-a gradient differentiates pulmonary from extrapulmonary causes of hypoxemia:

A-a Gradient Calculation

Step 1: Calculate alveolar oxygen (PAO2):
PAO2 = (FiO2 × [Patm - PH2O]) - (PaCO2 / 0.8)
At sea level on room air: PAO2 = (0.21 × [760 - 47]) - (PaCO2 / 0.8) = 150 - (PaCO2 / 0.8)

Step 2: Calculate A-a gradient:
A-a gradient = PAO2 - PaO2

Normal A-a gradient: (Age / 4) + 4 mmHg
Example: 60-year-old → (60/4) + 4 = 19 mmHg

A-a Gradient Interpretation

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A-a Gradient Interpretation Causes
Normal (<20 mmHg in young adults) Extrapulmonary cause Hypoventilation, low FiO2 (altitude)
Elevated (>normal for age) Pulmonary gas exchange abnormality V/Q mismatch, shunt, diffusion impairment
Severely elevated (>50 mmHg) Severe gas exchange impairment ARDS, severe pneumonia, large shunt
Normal A-a Gradient Rule of Thumb

A-a gradient = (Age / 4) + 4. For a 40-year-old: (40/4) + 4 = 14 mmHg. For an 80-year-old: (80/4) + 4 = 24 mmHg. This adjusts for normal age-related decline in gas exchange. A-a gradient >normal indicates pulmonary pathology (not just hypoventilation or altitude).

P/F Ratio (PaO2/FiO2 Ratio)

The P/F ratio normalizes PaO2 for inspired oxygen concentration, essential for ARDS diagnosis and assessment of oxygenation on supplemental O2:

P/F Ratio Calculation

P/F Ratio = PaO2 / FiO2

Example 1: PaO2 90 mmHg on room air (FiO2 0.21)
P/F Ratio = 90 / 0.21 = 429 (normal)

Example 2: PaO2 90 mmHg on 50% oxygen (FiO2 0.50)
P/F Ratio = 90 / 0.50 = 180 (severe ARDS)

P/F Ratio Interpretation - ARDS (Berlin Criteria)

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ARDS Severity P/F Ratio Clinical Significance
Normal >400 Normal oxygenation
Mild ARDS 200-300 Mild oxygenation impairment with PEEP ≥5
Moderate ARDS 100-200 Moderate oxygenation impairment with PEEP ≥5
Severe ARDS <100 Severe oxygenation impairment with PEEP ≥5
ARDS Berlin Criteria (2012)

P/F ratio <300 with bilateral infiltrates on CXR, within 1 week of known insult, respiratory failure not fully explained by cardiac failure or fluid overload. PEEP ≥5 cmH2O required for classification. Severity impacts mortality: Mild (27%), Moderate (32%), Severe (45%).

Oxygen-Hemoglobin Dissociation Curve

The sigmoid-shaped curve describes the relationship between PaO2 and hemoglobin oxygen saturation (SaO2):

Key Features of the Curve

  • Plateau phase (PaO2 60-100 mmHg): SaO2 remains >90%; steep decline below PaO2 60 mmHg
  • P50 (normal = 27 mmHg): PaO2 at which hemoglobin is 50% saturated; indicates oxygen affinity
  • Clinical significance: Large PaO2 drops from 100→80 mmHg cause minimal SaO2 change, but 60→40 mmHg drops SaO2 dramatically

Rightward Shift (Decreased Oxygen Affinity - Easier O2 Release)

  • Effect: Lower SaO2 at same PaO2; hemoglobin releases oxygen more readily to tissues
  • Causes: Acidosis (↓pH), hypercapnia (↑CO2), hyperthermia (fever), increased 2,3-DPG
  • Mnemonic: "CADET, face RIGHT" = CO2, Acidosis, 2,3-DPG, Exercise (lactic acid), Temperature
  • Clinical benefit: Improves tissue oxygen delivery despite same PaO2

Leftward Shift (Increased Oxygen Affinity - Harder O2 Release)

  • Effect: Higher SaO2 at same PaO2; hemoglobin binds oxygen tightly and releases less to tissues
  • Causes: Alkalosis (↑pH), hypocapnia (↓CO2), hypothermia, decreased 2,3-DPG, fetal hemoglobin, carbon monoxide
  • Clinical problem: Despite normal SaO2, tissues receive less oxygen (impaired unloading)
  • CO poisoning: Leftward shift plus direct SaO2 reduction creates severe tissue hypoxia despite normal PaO2
Clinical Application of Curve Shifts

In septic shock with lactic acidosis and fever, rightward shift helps compensate by enhancing tissue oxygen extraction. In contrast, hypothermic patients post-cardiac arrest have leftward shift, impairing oxygen delivery despite adequate PaO2. Avoid hyperventilation causing hypocapnia and leftward shift in TBI patients.

Interfering Factors

Pre-Analytical Factors Affecting PaO2

  • Air bubbles in sample: Room air (PO2 ~150 mmHg) mixes with sample, falsely elevating PaO2
  • Delayed analysis: Cellular metabolism consumes oxygen; PaO2 decreases ~5-10 mmHg per hour at room temperature
  • Sample on ice: Slows cellular metabolism; analyze within 30 minutes even if iced
  • Excessive heparin: Liquid heparin dilutes sample and contains dissolved oxygen, altering PaO2
  • Venous contamination: Inadequate arterial sample contains venous blood; falsely lowers PaO2
  • Temperature correction: Hypothermia decreases PaO2; most labs report at 37°C regardless of patient temperature

Patient Factors

  • FiO2 variation: PaO2 varies directly with inspired oxygen; document FiO2 at time of ABG
  • Position changes: Supine position decreases PaO2 by 5-10 mmHg vs upright (basilar atelectasis)
  • Altitude: High altitude reduces atmospheric pressure and PaO2; normal <80 mmHg above 5,000 feet
  • Anxiety/hyperventilation: Increased ventilation may temporarily improve PaO2 in V/Q mismatch
  • PEEP/CPAP effect: Positive pressure recruits alveoli and improves PaO2; note ventilator settings

Clinical Conditions Affecting Interpretation

  • Carbon monoxide poisoning: PaO2 normal but oxygen delivery impaired (CO occupies Hb binding sites); calculate oxygen content, not just PaO2
  • Severe anemia: Normal PaO2 but reduced oxygen-carrying capacity; low oxygen content despite adequate PaO2
  • Methemoglobinemia: PaO2 normal but SaO2 reduced (methemoglobin cannot bind oxygen); suspect with "chocolate brown" blood
  • Polycythemia: Normal PaO2 but increased oxygen-carrying capacity; hyperviscosity may impair microcirculation

Technical/Measurement Issues

  • Pulse oximetry vs ABG: SpO2 estimates SaO2 but does not measure PaO2; can be falsely normal in CO poisoning, methemoglobinemia
  • Calculated vs measured SaO2: ABG machines measure PaO2 and calculate SaO2 from dissociation curve; may be inaccurate if abnormal hemoglobin
  • Quality control: Malfunctioning ABG analyzer or expired calibration solutions affect accuracy
Clinical Pearls
"PaO2 <60 mmHg needs supplemental oxygen"

This is the critical threshold on the oxygen-hemoglobin dissociation curve. Below 60 mmHg, the curve steepens and SaO2 drops rapidly. PaO2 <60 mmHg corresponds to SaO2 <90% and represents an absolute indication for oxygen therapy.

"A-a gradient differentiates causes of hypoxemia"

Normal A-a gradient (age/4 + 4) with hypoxemia means hypoventilation or low FiO2 - look for high PaCO2 or altitude. Elevated A-a gradient means pulmonary pathology (V/Q mismatch, shunt, diffusion impairment). Simple calculation excludes or implicates the lungs.

"Five causes of hypoxemia" - VSHD-L

V/Q mismatch (most common, responds to O2), Shunt (refractory to 100% O2), Hypoventilation (normal A-a gradient + high CO2), Diffusion impairment (worsens with exercise), Low FiO2 (altitude, fire). Knowing these five mechanisms guides diagnosis and treatment.

"Normal A-a gradient rule = age/4 + 4"

Quick bedside calculation. 40-year-old: (40/4) + 4 = 14 mmHg. 80-year-old: (80/4) + 4 = 24 mmHg. If measured A-a gradient exceeds this, patient has pulmonary pathology. If A-a gradient is normal despite hypoxemia, cause is extrapulmonary (hypoventilation or altitude).

"P/F ratio <300 = ARDS"

Berlin Criteria define ARDS as P/F ratio <300 with bilateral infiltrates and known insult within 1 week. Mild ARDS = P/F 200-300, Moderate = 100-200, Severe <100. P/F ratio standardizes PaO2 across varying FiO2, essential for mechanically ventilated patients.

"Rightward shift = easier oxygen release to tissues"

Acidosis, hypercapnia, fever, and elevated 2,3-DPG shift curve right. Hemoglobin releases oxygen more readily despite same PaO2. In sepsis, this is beneficial adaptation. Mnemonic: "CADET, face RIGHT" = CO2, Acidosis, 2,3-DPG, Exercise, Temperature.

"Leftward shift = tighter oxygen binding, impaired tissue delivery"

Alkalosis, hypocapnia, hypothermia, and CO poisoning shift curve left. Despite normal or high SaO2, tissues receive less oxygen. Avoid hyperventilation in head injury - leftward shift from hypocapnia worsens cerebral hypoxia despite maintaining PaO2.

"Shunt doesn't respond to 100% oxygen"

Hallmark of shunt physiology. If PaO2 fails to rise above 400-500 mmHg on 100% FiO2, significant shunt exists (>30% shunt fraction). Blood bypassing alveoli cannot be oxygenated. Seen in ARDS, severe pneumonia, pulmonary AVM. Calculate shunt fraction or use empiric PEEP recruitment.

"Age-adjusted PaO2 = 104 - (0.27 × age)"

PaO2 declines 0.27 mmHg per year. For 70-year-old: 104 - (0.27 × 70) = 85 mmHg (normal lower limit). Don't overcall hypoxemia in elderly. Conversely, PaO2 75 mmHg in 30-year-old is abnormal and warrants investigation.

"Always interpret PaO2 with FiO2"

PaO2 90 mmHg on room air is normal; same value on 100% FiO2 represents severe hypoxemia (shunt). Use P/F ratio (PaO2/FiO2) to standardize. Normal P/F >400; <300 defines ARDS. P/F ratio allows comparison across varying oxygen supplementation.

"CO poisoning - normal PaO2, low oxygen delivery"

Carbon monoxide binds hemoglobin with 240× affinity vs oxygen. PaO2 measures dissolved oxygen (normal), but SaO2 is reduced (CO occupies Hb sites) and dissociation curve shifts left (impaired unloading). Calculate oxygen content = (1.34 × Hb × SaO2) + (0.003 × PaO2). Treat with 100% O2 or hyperbaric O2.

"ABG sample handling matters"

Air bubbles falsely elevate PaO2 (room air PO2 ~150 mmHg). Delayed analysis lowers PaO2 (cells consume oxygen ~10 mmHg/hour). Ice slows metabolism but doesn't stop it. Analyze within 15 minutes at room temperature or 30 minutes if iced. Expel all air bubbles.

"Pulse oximetry is NOT PaO2"

SpO2 estimates SaO2, not PaO2. Due to flat portion of dissociation curve, SpO2 can be 95% with PaO2 anywhere from 70-100 mmHg. SpO2 also unreliable in CO poisoning (falsely normal), methemoglobinemia, severe anemia, poor perfusion, dark nail polish. ABG required for definitive oxygenation assessment.

References
  1. Kratz, A., Ferraro, M., Sluss, P. M., & Lewandrowski, K. B. (2004). Laboratory reference values. New England Journal of Medicine, 351, 1548-1564.
  2. Lee, M. (Ed.). (2009). Basic skills in interpreting laboratory data. Ashp.
  3. Farinde, A. (2021). Lab values, normal adult: Laboratory reference ranges in healthy adults. Medscape. https://emedicine.medscape.com/article/2172316-overview?form=fpf
  4. Nickson, C. (n.d.). Critical Care Compendium. Life in the Fast Lane • LITFL. https://litfl.com/ccc-critical-care-compendium/
  5. Farkas, Josh MD. (2015). Table of Contents - EMCrit Project. EMCrit Project. https://emcrit.org/ibcc/toc/
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