Oxygenation/Oxygen Transport

Measures of Oxygenation

• PaO₂: Partial pressure of oxygen in arterial blood: normal value is ~90 mmHg

• PAO₂: Partial pressure of oxygen in the avleoli: normal value is ~100 mmHg.

  • Determined by alveolar gas equation: PAO₂= FiO₂ (P_atm - P_H2O) - PaCO₂/R where P_atm= atmospheric pressure (generally 760mmHg unless at altitude), P_H2O= 47 mmHg and R is the respiratory quotient (CO2 produced per oxygen consumed)

  • R= 0.8 on a normal diet, 1 with all carbohdyrate diet, 0.7 with all fat diet, and >1 when lipogenesis (i.e. with overfeeding) is occurring

• Aa gradient: The difference between the alveolar and arterial partial pressure of oxygen= PAO₂-PaO₂ . The normal value for the Aa gradient is 5-10 and increases with age [(Age+ 4)/4 in adults]

  • The normal Aa gradient is due to intrinsic shunt existing in healthy human beings (ie Thebesian veins, bronchial veins which drain venous blood into the left side of the heart as well as likely microatelectasis and thus natural intrapulmonary shunt)

  • Helps identify causes of hypoxemia:

    • Normal Aa gradient:

      • Decreased Inspired Oxygen (i.e. due to altitude or subambient oxygen delivery)

      • Hypoventilation

    • Increased Aa gradient:

      • Shunt (can be intracardiac as in right to left shunt or intrapulmonary)

      • VQ mismatch (on the same continuum as shunt)

      • Diffusion impairment (very rare to see, especially in children, can sometimes be seen during exercise and higher cardiac output as not enough time for oxygen loading to occur at the avleolar/capillary interface

  • A quick primer on the Aa gradient

• P/F ratio: Ratio of PaO2 to FiO2. The lower the number the more severe the impairment in oxygenation.

  • Current Berlin Criteria use the P/F ratio to define and classify ARDS in adults

    • PF ratio < 101= severe ARDS

    • PF ratio 101-200= moderate ARDS

    • PF ratio 201-300= mild ARDS

• OI: Oxygenation index. OI= P_aw * FiO₂ / PaO₂ *100. This is primarily used as a number to trend the degree of impairment in oxygenation and incorporates the mean airway pressure (P_aw), a distinct advantage over the P/F ratio. In fact, the Pediatric Acute Lung Injury Consensus Conference to define pediatric ARDS utilized OI for their definition:

  • • Mild ARDS: OI of 4 to <8

    • Moderate ARDS: 8 to to <16

    • Severe ARDS: OI of >16.

    • OI 20-25= consideration of HFOV

    • OI 40= consideration of ECMO (in neonatal population)

  • No formal guidelines exist for transition from conventional ventilation to HFOV to ECMO in the pediatric population

• OSI: Oxygen saturation index= P_aw*FiO₂ /SpO2 : Similar to OI but used when PaO₂ not available (roughly 6.5 and 7.8 for ALI and ARDS, respectively)

• S/F ratio: SaO₂/FiO₂= similar to P/F ratio but used when no PaO₂ not available (roughly 253 for ALI and 212 for ARDS)-- technically requires oxygen saturation <97% as otherwise, you cannot be sure of what FiO2 is actually required (ie a 100% saturation could be a PaO2 of 95 or a PaO2 of 600 which would take very different FiO2's to produce

• PaO2 can be estimated from SaO2 via the hemoglobin oxygen dissociation curve:

Figure 1: Hemoglobin Oxygen Saturation Curve

Physiology

• Oxygen delivery is determined by the total arterial oxygen content and the cardiac output. This can be thought of as a train with boxcars where the total oxygen content represents the oxygen being carried on the hemoglobin boxcars and the train engine is the cardiac output.

DO2 =CaO2 X CO where DO₂ = Oxygen delivery, CaO₂=arterial oxygen content, and CO= cardiac output

CaO2= Hgb(Sat)(1.34) + 0.003(PaO2)

• As seen in the equation for oxygen content, PaO2 makes little contribution unless a patient is extremely anemic. Arterial oxygen content depends almost entirely upon Hgb and O₂ Saturation.

CO= SV X HR

• The body normally extracts only about 25% of the oxygen delivered to the tissues overall. This varies by organ but overall (i.e. the heart extracts a lot of oxygen but the kidneys utilize little oxygen-see figure 3 below), the extraction is about 25%.

• As the oxygen delivery decreases (or as oxygen demand increases), the body responds by extracting more oxygen and hence, the ScvO2 (oxygen saturation of blood at the SVC-RA junction) gradually decreases to reflect this increasing oxygen extraction. However, the body can only extract so much oxygen and eventually, a critical extraction threshold is met and cellular metabolism becomes anaerobic with the subsequent production of lactate. This occurs at the cellular level and there is tissue and intra-tissue variation in terms of when this threshold is met. (Figure 4 Below)

Figure 2: Oxygen Delivery and Extraction: Train and Boxcar analogy

Figure 3: Oxygen Extraction Varies by Organ

Figure 4: Oxygen delivery and Consumption

Treatment

• Global impairment in oxygen delivery can thus be determined by monitoring central venous oxygen saturation (measured at SVC-RA junction with a central venous line) or mixed venous oxygen saturation (measured with a Swan Ganz catheter at the pulmonary artery).

• Normal ScvO₂ = 70-75%, reflecting 25-30% extraction.

• Increased extraction (and thus decreased ScvO₂) generally reflects either decreased O₂ delivery or increased O₂ demand

• Decreased extraction (and thus elevated ScvO₂) can reflect paralysis/sedation, impaired tissue uptake (ie mitochondrial toxicity), or sometimes a diffusely vasoplegic and hyperdnyamic state where Hgb transit time through the capillary is such that time is not sufficient for adequate oxygen extraction

• Treatment includes:

  • Improve O₂ delivery: DO2 =CaO2 X CO

    • Increase oxygen content by increasing hemoglobin or oxygen saturation

    • Increase cardiac output by improving contractility, reducing afterload, or increasing heart rate (already increased in most patients with impaired oxygen delivery)

  • Decrease O₂ demand:

    • Endotracheal intubation (takes away work of breathing which can be substantial)

    • Sedation

    • Paralytic

    • Cooling (or maintaining normothermia and avoiding fever at least)