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Fraction of inspired oxygen

The fraction of inspired oxygen (FiO₂) is the concentration of oxygen in the gas mixture inhaled by a , expressed as a decimal fraction or , with room air containing 0.21 (21%) oxygen under standard atmospheric conditions. It represents the proportion of oxygen delivered via respiratory support systems, ranging from 0.21 to 1.0 (100%), and serves as a fundamental parameter for evaluating and optimizing pulmonary in medical practice. In clinical settings, FiO₂ is adjusted using devices such as nasal cannulas, , or mechanical ventilators to prevent while avoiding , which can lead to if prolonged exposure exceeds 0.50 (50%). Monitoring FiO₂ alongside metrics like arterial oxygen partial pressure (PaO₂) or peripheral oxygen saturation (SpO₂) guides therapy in conditions such as acute respiratory distress syndrome (ARDS), postoperative recovery, and neonatal care, where targets often aim for SpO₂ between 90% and 95% to balance oxygenation and minimize complications like . The measurement of FiO₂ relies on oxygen analyzers in controlled environments or estimations based on delivery system flow rates, with high-flow systems providing more precise control compared to low-flow options. In intensive care, FiO₂ is often titrated downward as patient stability improves, typically to below 0.50 within 12–24 hours post-intubation, to reduce risks of absorption and free radical damage.

Fundamentals

Definition

The fraction of inspired oxygen (FiO2) is defined as the volumetric or fraction of oxygen in the gas mixture that is inhaled by an individual. It quantifies the concentration of oxygen relative to the total volume of inspired air and is typically expressed as a between 0 and 1 (e.g., 0.21) or as a (21%). Unlike measures of , such as the arterial partial pressure of oxygen (PaO2) or the inspired partial pressure of oxygen (PiO2), FiO2 specifically denotes the proportional concentration of oxygen in the inspired gas, independent of ambient pressure variations. This distinction is crucial in respiratory physiology, as FiO2 focuses on composition rather than the pressure exerted by oxygen molecules. FiO2 is relevant across various settings, including breathing ambient air at , where it naturally equals 0.21, as well as in clinical scenarios involving supplemental oxygen via masks or cannulas, or during where precise oxygen blending allows FiO2 adjustment from 0.21 up to 1.0 (100%).

Normal Values and Measurement

In ambient air at , the fraction of inspired oxygen (FiO₂) is 0.21, equivalent to 21% oxygen content in dry room air. This standard value represents the proportion of oxygen molecules in the inspired gas mixture under normal atmospheric conditions. introduces a minor variation by diluting the oxygen fraction, as displaces some oxygen; for instance, at 100% relative humidity and body , the effective FiO₂ can decrease to approximately 0.20. At higher altitudes, the FiO₂ fraction remains 0.21 in dry air, though the of inspired oxygen declines due to reduced barometric , impacting overall oxygenation. In clinical settings, supplemental oxygen delivery elevates FiO₂ to ranges of 0.24–1.00 (24–100%), depending on the device used, such as nasal cannulas (typically 0.24–0.44), face masks (0.35–0.80), or mechanical ventilators (up to 1.00). These ranges allow for targeted increases in inspired oxygen to meet patient needs, with ventilators providing the most precise control over FiO₂ levels. FiO₂ is measured directly in delivered gases using oxygen analyzers equipped with paramagnetic or electrochemical () sensors. Paramagnetic sensors detect oxygen based on its , where oxygen molecules are drawn into a , causing measurable deflection proportional to concentration. Fuel cell sensors, conversely, produce an electrical current through an electrochemical reaction with oxygen, calibrated to quantify or percentage. In non-invasive therapies like nasal cannulas, FiO₂ is indirectly estimated from flow rates and device specifications rather than measurement, as direct sampling is impractical. Accuracy of FiO₂ measurement and delivery can be influenced by several factors, including sensor calibration, which must be performed regularly to account for drift or environmental changes. Leaks in oxygen delivery systems, such as around masks or circuits, can significantly reduce the actual FiO₂ reaching the patient by entraining room air. Patient-specific variables, including breathing patterns like and , further affect delivered FiO₂, particularly in low-flow systems where entrainment of ambient air varies with inspiratory demand.

Physiological Role

Gas Exchange Basics

Gas exchange in the lungs primarily occurs at the alveolar-capillary interface, where oxygen from inspired air diffuses into the pulmonary to support systemic oxygenation. The fraction of inspired oxygen (FiO2) plays a central role in this process by determining the oxygen concentration available for mixing with residual gases in the alveoli during . In normal conditions, inspired air with an FiO2 of 0.21 mixes with alveolar gases, resulting in an alveolar oxygen (PAO2) that facilitates efficient oxygen uptake. Once in the alveoli, oxygen diffuses across the thin alveolar epithelium and capillary endothelium into the deoxygenated blood in pulmonary capillaries, driven by a gradient between the alveoli and blood. This diffusion is highly efficient under physiological conditions, with oxygen equilibrating rapidly as blood traverses the capillary bed. The magnitude of this gradient is directly influenced by FiO2; higher FiO2 increases PAO2, thereby enhancing the driving force for diffusion and improving oxygen to hemoglobin in erythrocytes. Hypoxemia, characterized by reduced arterial oxygen (PaO2), can arise from low FiO2, which limits the oxygen available for alveolar filling and subsequent , as seen in high-altitude environments where ambient oxygen is scarce. impairment, such as from alveolar-capillary membrane thickening due to or , further exacerbates hypoxemia by slowing oxygen transfer, particularly when FiO2 is low and the gradient is insufficient to compensate. Similarly, intrapulmonary or intracardiac shunts cause hypoxemia by allowing deoxygenated blood to bypass ventilated alveoli, rendering supplemental FiO2 less effective in correcting the deficit since shunted blood does not encounter oxygenated air. Effective also depends on ventilation-perfusion (V/Q) matching, where alveolar aligns with pulmonary blood flow to optimize oxygen uptake. Regional V/Q mismatches, such as low V/Q ratios in poorly ventilated but perfused areas, reduce overall oxygenation efficiency, but increasing FiO2 can modulate arterial oxygenation by elevating PAO2 and compensating for mild mismatches. In contrast, severe mismatches like shunts show limited improvement with FiO2 adjustments, highlighting FiO2's variable impact on arterial PaO2 based on underlying physiological integrity.

Alveolar Gas Equation

The alveolar gas equation provides a for estimating the of oxygen in the alveoli (PAO₂), which is crucial for linking the fraction of inspired oxygen (FiO₂) to alveolar oxygenation during steady-state . The equation is derived from principles of and the , assuming that the volume of oxygen consumed equals the volume of produced adjusted by the (R), with acting as an inert diluent gas to maintain alveolar volume stability. The full equation is: PAO_2 = FiO_2 \times (P_B - P_{H_2O}) - \frac{PaCO_2}{R} where P_B is the barometric pressure (typically 760 mmHg at ), P_{H_2O} is the pressure (approximately 47 mmHg at body temperature), PaCO_2 is the arterial of (approximating alveolar PCO₂), and R is the (typically 0.8 for a mixed ). Derivation begins with the mass balance for oxygen and carbon dioxide in the alveoli under steady-state conditions, where inspired alveolar ventilation (\dot{V}_{A_I}) and expired alveolar ventilation (\dot{V}_{A_E}) differ due to net gas exchange. For oxygen, the balance is \dot{V}_{O_2} = F_{I_{O_2}} \cdot \dot{V}_{A_I} - F_{A_{O_2}} \cdot \dot{V}_{A_E}, and for carbon dioxide, \dot{V}_{CO_2} = F_{A_{CO_2}} \cdot \dot{V}_{A_E}, with the respiratory quotient defined as R = \dot{V}_{CO_2} / \dot{V}_{O_2}. Nitrogen balance, assuming no net exchange (\dot{V}_{N_2} = F_{I_{N_2}} \cdot \dot{V}_{A_I} = F_{A_{N_2}} \cdot \dot{V}_{A_E}), relates inspired and expired volumes: \dot{V}_{A_E} = \dot{V}_{A_I} \cdot (1 - F_{I_{O_2}} + F_{I_{N_2}}). Substituting and rearranging yields the fractional form F_{A_{O_2}} = F_{I_{O_2}} - F_{A_{CO_2}} \cdot (1 - F_{I_{O_2}}) / R, which converts to partial pressures using Dalton's law (P_{A_{O_2}} = F_{A_{O_2}} \cdot (P_B - P_{H_2O})) after adjusting for inspired oxygen pressure (P_{I_{O_2}} = F_{I_{O_2}} \cdot (P_B - P_{H_2O})) and assuming negligible inspired CO₂. Key assumptions include steady-state metabolism (no net accumulation of gases), inertness of (constant across inspiration and expiration), a constant (typically 0.8, varying with diet from 0.7 for fats to 1.0 for carbohydrates), and dry gas measurements before humidification; the is a simplification of the ideal alveolar gas equation, which assumes perfect uniformity in alveolar gas composition and neglects minor gas exchanges like CO₂ in inspired air. These assumptions hold reasonably at normoxic FiO₂ levels but may introduce errors at low FiO₂ or high altitudes. In , the equation enables estimation of PAO₂ to evaluate oxygenation efficiency, such as by calculating the (A-a = PAO₂ - PaO₂), which normally ranges from 5-15 mmHg and increases with impaired , aiding assessment of ventilation-perfusion matching without direct alveolar sampling.

Clinical Applications

involves the administration of supplemental oxygen to experiencing , primarily through non-invasive delivery systems that adjust the fraction of inspired oxygen (FiO2) to improve oxygenation without . Common delivery methods include the , which provides low-flow oxygen at rates of 1 to 6 L/min, achieving FiO2 levels of approximately 0.24 to 0.44 depending on and patterns. The delivers oxygen at 5 to 10 L/min, typically yielding FiO2 of 0.35 to 0.50, while the , equipped with a bag, can supply higher concentrations up to 0.80 to 0.90 at flows of 10 to 15 L/min when properly fitted. High-flow nasal cannula (HFNC) systems deliver heated and humidified oxygen at flows of 20 to 60 L/min, achieving FiO₂ levels from 0.21 to 1.00 with precise blender control, suitable for moderate to severe . These systems are selected based on the required FiO2 and tolerance, with nasal cannulas preferred for comfort in settings and masks for more acute needs. Indications for non-invasive oxygen therapy center on correcting hypoxemia arising from conditions such as , acute exacerbations of (COPD), or congestive , where arterial oxygen saturation (SaO2) or peripheral oxygen saturation (SpO2) falls below 90%. In these scenarios, aims to restore adequate tissue oxygenation while minimizing complications, with target SpO2 levels generally set at 94% to 98% for most patients and 88% to 92% for those with COPD to avoid suppressing respiratory drive. For instance, in pneumonia-induced , oxygen supplementation supports impaired by alveolar consolidation, and in heart failure, it addresses ventilation-perfusion mismatches leading to low PaO2. Prolonged exposure to high FiO2 levels exceeding 0.60 can result in , manifesting as , reduced , and inflammatory lung injury after 24 hours or more at normal . Additionally, elevated FiO2 promotes absorption by accelerating nitrogen washout from alveoli, causing collapse and increased shunt fraction, which worsens ventilation-perfusion matching. These risks underscore the need for the lowest effective FiO2 to achieve therapeutic goals. Monitoring during relies on to continuously assess SpO2 and guide FiO2 titration, ensuring oxygenation targets are met without inducing , which can exacerbate . In vulnerable populations, such as preterm infants, strict avoidance of is critical, as even brief exposures to FiO2 above 0.40 increase the risk of and , necessitating precise adjustments to maintain SpO2 between 90% and 95%. This approach integrates FiO2's role in alveolar to prevent both and iatrogenic harm.

Mechanical Ventilation

In mechanical ventilation, the fraction of inspired oxygen (FiO₂) serves as a critical parameter for maintaining adequate oxygenation in patients with respiratory failure. Modern ventilators enable precise adjustment of FiO₂ from 0.21 (equivalent to room air) to 1.00 (pure oxygen), allowing clinicians to tailor delivery based on patient needs. Upon initiating invasive mechanical ventilation, FiO₂ is typically set at 1.00 to swiftly address severe hypoxemia, followed by gradual weaning guided by arterial blood gas (ABG) results to target a partial pressure of arterial oxygen (PaO₂) of 55–80 mmHg or oxygen saturation (SpO₂) of 88–95%. This approach balances rapid correction of hypoxia with the need to avoid excessive oxygen exposure. FiO₂ adjustments are integrated into common ventilation modes, such as volume-controlled ventilation (VCV), which delivers a fixed regardless of airway , and pressure-controlled ventilation (PCV), which maintains a set inspiratory to limit peak pressures. In both modes, FiO₂ is often paired with (PEEP) to enhance alveolar recruitment, improve ventilation-perfusion matching, and optimize without solely relying on high oxygen concentrations. For instance, increasing PEEP can allow for lower FiO₂ settings while achieving equivalent oxygenation, promoting lung protection during prolonged support. Clinical guidelines, notably the ARDSNet protocol from the Clinical Trials Network, emphasize conservative FiO₂ management to mitigate ventilator-induced lung injury (VILI). This protocol advocates limiting FiO₂ to 0.60 or below through incremental PEEP adjustments (starting at a minimum of 5 cm H₂O) to maintain oxygenation goals, as higher FiO₂ levels increase the risk of and . Implementation of this strategy in patients with (ARDS) has demonstrated reduced mortality and increased ventilator-free days compared to traditional higher approaches. Prolonged high FiO₂ during contributes to complications, primarily through , where excessive damage pulmonary and , leading to , absorption atelectasis, and acute lung injury. Additionally, elevated FiO₂ can exacerbate by promoting alveolar overdistension and inflammation in synergy with mechanical pressures, increasing the incidence of and other air leaks. These risks underscore the importance of vigilant and to the lowest effective FiO₂.

Diagnostic Metrics

PaO2/FiO2 Ratio

The PaO2/FiO2 ratio, often abbreviated as P/F ratio, is defined as the ratio of the (PaO2), measured in millimeters of mercury (mmHg) via gas , to the fraction of inspired oxygen (FiO2), expressed as a value between 0 and 1. This metric quantifies the efficiency of pulmonary oxygenation and assesses lung function in a manner that accounts for the level of supplemental oxygen provided, making it particularly useful in critical care settings for patients receiving varying degrees of oxygen support. The ratio is calculated using the formula: \mathrm{P/F\ ratio} = \frac{\mathrm{PaO_2\ (mmHg)}}{\mathrm{FiO_2\ (decimal)}} For example, if a patient's gas shows a PaO2 of 80 mmHg while receiving an FiO2 of 0.50, the P/F ratio is 80 / 0.50 = 160. FiO2 values are determined based on the oxygen delivery system, such as 0.21 for room air or up to 1.0 for 100% oxygen via . In the Definition of (ARDS), established in 2012, the P/F ratio serves as a key criterion for stratifying disease severity, with thresholds of mild ARDS for 200 mmHg < P/F ≤ 300 mmHg, moderate ARDS for 100 mmHg < P/F ≤ 200 mmHg, and severe ARDS for P/F ≤ 100 mmHg, all measured with a minimum positive end-expiratory pressure of 5 cm H2O. This definition has been expanded by the 2023 Global Definition of ARDS, which retains similar P/F thresholds for intubated patients but includes SpO2/FiO2 surrogates and criteria for non-intubated patients on high-flow nasal oxygen or , improving applicability in resource-limited settings. One primary advantage of the P/F ratio is its ability to stratify the severity of independently of the administered FiO2 level, allowing consistent comparison across patients on different oxygen therapies.

Interpretation and Limitations

The PaO2/FiO2 ratio serves as a key diagnostic and prognostic tool in assessing oxygenation impairment, with established thresholds guiding clinical classification. In healthy individuals at , the ratio typically exceeds 400–500 mmHg, reflecting efficient pulmonary under normal conditions. Values between 200 and 300 mmHg indicate mild hypoxemic , often aligning with the mild category of (ARDS) as per the Berlin definition, which requires a minimum (PEEP) of 5 cmH2O for categorization. Moderate impairment falls between 100 and 200 mmHg, while ratios ≤100 mmHg denote severe ARDS, correlating with progressively higher risks of complications. This metric is integrated into scoring systems for , where it contributes to the respiratory component of the Sequential Organ Failure Assessment () score to evaluate severity, and in trauma assessment via tools like the Thorax Trauma Severity Score (TTSS), which incorporates the ratio to predict outcomes in patients. Despite its utility, the PaO2/FiO2 ratio has notable limitations that can affect its reliability across clinical scenarios. It is highly sensitive to ventilator settings, particularly PEEP levels, as higher PEEP recruits alveoli and improves oxygenation, potentially inflating the ratio and altering ARDS severity classification without reflecting true underlying lung pathology. The ratio also underestimates impairment at higher altitudes due to reduced barometric pressure, which lowers PaO2 for a given FiO2 and shunt fraction, necessitating altitude-adjusted calculations in such environments. Furthermore, it serves as an indirect surrogate for intrapulmonary shunt and can be misleading when mixed venous oxygen tension is elevated, masking significant lung dysfunction, or in non-ARDS conditions like chronic obstructive pulmonary disease, where ventilation-perfusion mismatches confound interpretation. To address these drawbacks, alternatives such as the SpO2/FiO2 have been validated for use in settings without gas (ABG) availability, offering a non-invasive surrogate that correlates well with PaO2/FiO2 for ARDS screening and monitoring, particularly in resource-limited environments. Adjustments for PEEP, such as the proposed P/FP (PaO2 divided by FiO2 multiplied by PEEP in cmH2O), enhance prognostic accuracy by for ventilatory support intensity, outperforming the in predicting hospital mortality among ARDS patients. The PaO2/FiO2 ratio holds substantial prognostic value in (ICU) settings, where lower values independently predict increased mortality risk. In ARDS cohorts, ratios <100 mmHg are associated with approximately 45% mortality, compared to 27% for mild cases (200–300 mmHg), establishing a clear gradient of risk. Among septic patients, both extremely low (<150 mmHg) and high (>400 mmHg) ratios correlate with elevated 28-day mortality, reflecting hypoxemia-driven organ failure or potential . This predictive power underscores its role in ICU and resource allocation, though integration with other markers like SOFA enhances overall accuracy.

Mathematical Derivations

The shunt equation quantifies the fraction of cardiac output that bypasses pulmonary gas exchange, known as the pulmonary shunt fraction (Qs/Qt), and incorporates FiO2 indirectly through the calculation of end-capillary oxygen content (CcO2), which relies on alveolar oxygen tension (PAO2) derived from FiO2. The equation is expressed as: \frac{Q_s}{Q_t} = \frac{C_cO_2 - C_aO_2}{C_cO_2 - C_vO_2} where C_cO_2 is the oxygen content in end-pulmonary capillary blood, C_aO_2 is the arterial oxygen content, and C_vO_2 is the mixed venous oxygen content, all in mL O2/dL blood. This fraction typically ranges from 2-5% in healthy individuals but increases in conditions like atelectasis or pneumonia, reflecting impaired oxygenation despite elevated FiO2. To derive the shunt equation, consider total pulmonary blood flow (Qt) as the sum of shunted blood flow (Qs) and capillary blood flow (Qc), such that Qt = Qs + Qc. The total oxygen content delivered to the arterial system is then Qc × CcO2 + Qs × CvO2, which equals Qt × CaO2 under steady-state conditions. Rearranging yields CaO2 = (Qc/Qt) × CcO2 + (Qs/Qt) × CvO2. Solving for the shunt fraction (Qs/Qt) gives (CaO2 - CvO2) / (CcO2 - CvO2) = Qc/Qt, and since Qc/Qt = 1 - Qs/Qt, the final form is Qs/Qt = (CcO2 - CaO2) / (CcO2 - CvO2). FiO2 influences this derivation by determining PAO2, which assumes CcO2 reflects full equilibration with alveolar gas at that tension, typically calculated as CcO2 = (1.34 × Hb × SO2 at PAO2) + (0.003 × PAO2), where Hb is hemoglobin concentration and SO2 is oxygen saturation. The arterial oxygen content (CaO2) formula links FiO2 to systemic oxygen delivery by relating it to arterial (PaO2) and (SaO2), both of which increase with higher FiO2 in normal lungs: C_aO_2 = (1.34 \times [Hb](/page/HB) \times S_aO_2) + (0.003 \times P_aO_2) Here, the bound component (1.34 mL /g ) dominates, as dissolved oxygen is minimal, but SaO2 depends on PaO2 via the oxygen-hemoglobin dissociation curve, which in turn is influenced by FiO2 through alveolar gas dynamics. Normal CaO2 values are approximately 20 mL /dL at with of 15 g/dL. Variations in the (R), defined as R = VCO2 / VO2 (volume of CO2 produced to consumed), affect the alveolar gas equation and thus FiO2's role in PAO2 estimation, with R ≈ 0.8 on a mixed but ranging from 0.7 ( metabolism) to 1.0 (). This variability alters the PaCO2/R term, potentially leading to over- or underestimation of PAO2 by up to 10-20 mmHg if R deviates significantly from 0.8, impacting shunt and content calculations that rely on accurate FiO2-derived PAO2.

Calculation Examples

To illustrate the application of FiO2 in key computations, consider the following worked examples using standard physiological assumptions and equations. These demonstrate practical calculations for alveolar oxygen tension (PAO2), the PaO2/FiO2 ratio, and shunt fraction estimation, with step-by-step derivations including unit consistency and assumption verification. For the first example, compute PAO2 using the alveolar gas equation at FiO2 = 0.50, barometric pressure (PB) = 760 mmHg, pressure (PH2O) = 47 mmHg, arterial CO2 tension (PaCO2) = 40 mmHg, and (R) = 0.8. The equation is: PAO_2 = FiO_2 \times (PB - PH_2O) - \frac{PaCO_2}{R} All units are in mmHg, consistent for partial pressures; assumptions include sea-level conditions ( = 760 mmHg), body temperature of 37°C (PH2O = 47 mmHg), and steady-state ( = 0.8 for mixed ). First, calculate the inspired oxygen partial pressure: FiO_2 \times (PB - PH_2O) = 0.50 \times (760 - 47) = 0.50 \times 713 = 356.5 mmHg. Then, subtract the CO2 correction: \frac{PaCO_2}{R} = \frac{40}{0.8} = 50 mmHg. Thus, PAO_2 = 356.5 - 50 = 306.5 \approx 307 mmHg. This value represents expected alveolar oxygenation under supplemental oxygen, assuming no ventilation-perfusion mismatch. In the second example, calculate the PaO2/FiO2 ratio for a with arterial oxygen tension (PaO2) = 60 mmHg at FiO2 = 1.00 (100% oxygen). The is simply: \frac{PaO_2}{FiO_2} Units: PaO2 in mmHg, FiO2 as a decimal fraction (1.00); no conversions needed, as the is dimensionless. Substituting values: \frac{60}{1.00} = 60. According to the Berlin definition of (ARDS), a PaO2/FiO2 ≤100 mmHg with ≥5 cmH2O indicates severe ARDS, confirming significant oxygenation impairment here. Assumptions include accurate gas measurement and settings; the assumes steady-state conditions without major changes in FiO2 during sampling. For the third example, estimate the intrapulmonary shunt fraction (Qs/Qt) at FiO2 = 1.00, assuming hemoglobin (Hb) = 15 g/dL, PaO2 = 60 mmHg (arterial saturation SaO2 ≈90%), mixed venous PO2 (PvO2) = 40 mmHg (venous saturation SvO2 ≈75%), and PAO2 ≈663 mmHg (from alveolar gas equation as above, with end-capillary saturation ≈100%). The Berggren shunt equation is: \frac{Q_s}{Q_t} = \frac{C_cO_2 - C_aO_2}{C_cO_2 - C_vO_2} Oxygen contents (in mL O2/dL blood) use: bound O2 = 1.34 × Hb × (Sat/100), dissolved O2 = 0.003 × PO2 (mL/dL/mmHg). Units consistent (Hb in g/dL, PO2 in mmHg); assumptions verified: FiO2=1.00 minimizes diffusion effects, dissolved O2 significant at high PAO2, and saturations from standard oxyhemoglobin dissociation curve at pH 7.4, 37°C. Calculate end-capillary content (CcO2): bound = 1.34 × 15 × 1.00 = 20.10 mL/dL, dissolved = 0.003 × 663 ≈ 1.99 mL/dL, total CcO2 ≈ 22.09 mL/dL. Arterial content (CaO2): bound = 1.34 × 15 × 0.90 = 18.06 mL/dL, dissolved = 0.003 × 60 = 0.18 mL/dL, total CaO2 ≈ 18.24 mL/dL. Venous content (CvO2): bound = 1.34 × 15 × 0.75 = 15.08 mL/dL, dissolved = 0.003 × 40 = 0.12 mL/dL, total CvO2 ≈ 15.20 mL/dL. Thus, \frac{Q_s}{Q_t} = \frac{22.09 - 18.24}{22.09 - 15.20} = \frac{3.85}{6.89} \approx 0.56 or 56%, indicating substantial right-to-left shunting consistent with severe hypoxemia.