Rationale and limitations of the SpO2/FiO2 as a possible substitute for PaO2/FiO2 in different preclinical and clinical scenarios

Carvalho, Eduardo Butturini de; Leite, Thiago Ravache Sobreira; Sacramento, Raquel Ferreira de Magalhães; Nascimento, Paulo Roberto Loureiro do; Samary, Cynthia dos Santos; Rocco, Patrícia Rieken Macedo; Silva, Pedro Leme

doi:10.5935/0103-507X.20220013-en

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REVIEW ARTICLE • Rev. bras. ter. intensiva 34 (1) • Jan-Mar 2022 • https://doi.org/10.5935/0103-507X.20220013-en copy

Rationale and limitations of the SpO₂/FiO₂ as a possible substitute for PaO₂/FiO₂ in different preclinical and clinical scenarios

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Although the PaO 2/FiO 2 derived from arterial blood gas analysis remains the gold standard for the diagnosis of acute respiratory failure, the SpO2/FiO2 has been investigated as a potential substitute. The current narrative review presents the state of the preclinical and clinical literature on the SpO2/FiO2 as a possible substitute for PaO2/FiO2 and for use as a diagnostic and prognostic marker; provides an overview of pulse oximetry and its limitations, and assesses the utility of SpO2/ FiO2 as a surrogate for PaO2/FiO2 in COVID-19 patients. Overall, 49 studies comparing SpO2/FiO2 and PaO2/FiO2 were found according to a minimal search strategy. Most were conducted on neonates, some were conducted on adults with acute respiratory distress syndrome, and a few were conducted in other clinical scenarios (including a very few on COVID-19 patients). There is some evidence that the SpO2/ FiO2 criteria can be a surrogate for PaO2/FiO2 in different clinical scenarios. This is reinforced by the fact that unnecessary invasive procedures should be avoided in patients with acute respiratory failure. It is undeniable that pulse oximeters are becoming increasingly widespread and can provide costless monitoring. Hence, replacing PaO2/FiO2 with SpO2/FiO2may allow resourcelimited facilities to objectively diagnose acute respiratory failure.

Keywords:
COVID-19; SARS-CoV-2; Oxygen saturation; Oximetry; Blood gas analysis; Oxygen; Respiratory distress syndrome; Respiratory insufficiency; Prognosis; Infant; Infant newborn; Adult

Limitation	Characteristics	References
Anemia	Anemia may cause underestimation of SaO2 by SpO2 readings in hypoxemic patients. SpO2 can accurately represent SaO2 values in hematocrits as low as 10 - 14% in dogs	Zeserson et al.,(⁸8 Zeserson E, Goodgame B, Hess JD, Schultz K, Hoon C, Lamb K, et al. Correlation of venous blood gas and pulse oximetry with arterial blood gas in the undifferentiated critically ill patient. J. Intensive Care Med. 2018;33(3):176-81.) Hafen et al.,(¹⁴14 Hafen BB, Sharma S. Oxygen saturation. 2021 Aug 12. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022.) Schnapp et al.,(¹⁵15 Schnapp LM, Cohen NH. Pulse oximetry. Uses and abuses. Chest. 1990;98(5):1244-50.) Chan et al.,(¹⁶16 Chan ED, Chan MM, Chan MM. Pulse oximetry: understanding its basic principles facilitates appreciation of its limitations. Respir Med. 2013;107(6):789-99.) Lee et al.,(²⁰20 Lee S, Tremper KK, Barker SJ. Effects of anemia on pulse oximetry and continuous mixed venous hemoglobin saturation monitoring in dogs. Anesthesiology. 1991;75(1):118-22.) Jay et al.,(²¹21 Jay GD, Hughes L, Renzi FP. Pulse oximetry is accurate in acute anemia from hemorrhage. Ann Emerg Med. 1994;24(1):32-5.) Perkins et al.(²²22 Perkins GD, McAuley DF, Giles S, Routledge H, Gao F. Do changes in pulse oximeter oxygen saturation predict equivalent changes in arterial oxygen saturation? Crit Care. 2003;7(4):R67.) and Severinghaus et al.(²³23 Severinghaus JW, Koh SO. Effect of anemia on pulse oximeter accuracy at low saturation. J Clin Monit. 1990;6(2):85-8.)
Carbon monoxide intoxication	In the presence of carboxyhemoglobin, pulse oximeters consistently overestimate SpO2	Schnapp et al.(¹⁵15 Schnapp LM, Cohen NH. Pulse oximetry. Uses and abuses. Chest. 1990;98(5):1244-50.) and Barker et al.(²⁴24 Barker SJ, Tremper KK. The effect of carbon monoxide inhalation on pulse oximetry and transcutaneous PO2. Anesthesiology. 1987;66(5):677-9.)
Methemoglobinemia	SpO2 readings may decrease when methemoglobin levels rise, but when the latter reach 30 - 35%, PO readings reach a plateau of 80 - 85%	Schnapp et al.,(¹⁵15 Schnapp LM, Cohen NH. Pulse oximetry. Uses and abuses. Chest. 1990;98(5):1244-50.) Barker et al.(²⁵25 Barker SJ, Tremper KK, Hyatt J. Effects of methemoglobinemia on pulse oximetry and mixed venous oximetry. Anesthesiology. 1989;70(1):112-7.) and Eisenkraft(²⁶26 Eisenkraft JB. Pulse oximeter desaturation due to methemoglobinemia. Anesthesiology. 1988;68(2):279-82.)
High venous pressure	High venous pressure, for example in right heart systolic insufficiency or tricuspid valve regurgitation, may cause falsely low SpO2 values	Zeserson et al.,(⁸8 Zeserson E, Goodgame B, Hess JD, Schultz K, Hoon C, Lamb K, et al. Correlation of venous blood gas and pulse oximetry with arterial blood gas in the undifferentiated critically ill patient. J. Intensive Care Med. 2018;33(3):176-81.) Bucher et al.,(²⁷27 Bucher HU, Keel M, Wolf M, von Siebenthal K, Duc G. Artifactual pulseoximetry estimation in neonates. Lancet. 1994;343(8906):1135-6.) Fouzas et al.(²⁸28 Fouzas S, Priftis KN, Anthracopoulos MB. Pulse oximetry in pediatric practice. Pediatrics. 2011;128(4):740-52.) and Stewart et al.(29)
Dyes and pigments	Indigo carmine, indocyanine green, and methylene blue may alter SpO2 readings, since they cause tissue pigmentation, thereby altering light absorbance	Schnapp et al.(¹⁵15 Schnapp LM, Cohen NH. Pulse oximetry. Uses and abuses. Chest. 1990;98(5):1244-50.) and Fouzas et al.(²⁸28 Fouzas S, Priftis KN, Anthracopoulos MB. Pulse oximetry in pediatric practice. Pediatrics. 2011;128(4):740-52.)
Excessive motion	Artifacts caused by excessive motion can be interpreted as pulse signals and increase the noise-to-signal ratio	Schnapp et al.(¹⁵15 Schnapp LM, Cohen NH. Pulse oximetry. Uses and abuses. Chest. 1990;98(5):1244-50.) and Louie et al.(³⁰30 Louie A, Feiner JR, Bickler PE, Rhodes L, Bernstein M, Lucero J. Four types of pulse oximeters accurately detect hypoxia during low perfusion and motion. Anesthesiology. 2018;128(3):520-30.)
Hyperbilirubinemia	Although a case series reported overestimation of SaO2 by pulse oximeters in cirrhotic patients with hyperbilirubinemia, bilirubin has a different light absorption spectrum	Fouzas et al.,(²⁸28 Fouzas S, Priftis KN, Anthracopoulos MB. Pulse oximetry in pediatric practice. Pediatrics. 2011;128(4):740-52.) Nilles et al.,(³¹31 Nilles K, Subramanian R. 1187: Excessive hyperbilirubinemia interferes with pulse oximetric detection of hypoxemia in decompensated cirrhosis. Crit Care Med. 2012;40(12):1-328.) Salyer(³²32 Salyer JW. Neonatal and pediatric pulse oximetry. Respir Care. 2003;48(4):386-96; discussion 397-8.) and Veyckemans et al.(³³33 Veyckemans F, Baele P, Guillaume JE, Willems E, Robert A, Clerbaux T. Hyperbilirubinemia does not interfere with hemoglobin saturation measured by pulse oximetry. Anesthesiology. 1989;70(1):118-22.)
Hyperoxemia/hyperoxia	Pulse oximeters cannot detect hyperoxemia/hyperoxia, yet these events may evoke unwanted responses such as a decrease in cardiac output and heart rate (approximately 10%), 20% reduction in regional blood flow (cerebral, cardiac, skin, and skeletal muscle vascular beds), and a buildup of reactive oxygen species in the mitochondria, causing oxidative stress	Allardet-Servent et al.(³⁴34 Allardet-Servent J, Sicard G, Metz V, Chiche L. Benefits and risks of oxygen therapy during acute medical illness: Just a matter of dose! Rev Med Interne. 2019;40(10):670-6.) and Sjöberg et al.(³⁵35 Sjöberg F, Singer M. The medical use of oxygen: a time for critical reappraisal. J Intern Med. 2013;274(6):505-28.)
Low perfusion	Low perfusion due to hypovolemia, hypothermia, use of vasopressors, and peripheral vascular disease may lead to poor sensor readings, increasing the noise-to-signal ratio	Schnapp et al.(¹⁵15 Schnapp LM, Cohen NH. Pulse oximetry. Uses and abuses. Chest. 1990;98(5):1244-50.) and Fouzas et al.(²⁸28 Fouzas S, Priftis KN, Anthracopoulos MB. Pulse oximetry in pediatric practice. Pediatrics. 2011;128(4):740-52.)
External light sources	Although new pulse oximetry equipment can detect excessive light artifacts, there are reports of external light sources flooding the photodetector. Covering the sensor with an opaque material may prevent misreading	Schnapp et al.,(¹⁵15 Schnapp LM, Cohen NH. Pulse oximetry. Uses and abuses. Chest. 1990;98(5):1244-50.) Fouzas et al.(²⁸28 Fouzas S, Priftis KN, Anthracopoulos MB. Pulse oximetry in pediatric practice. Pediatrics. 2011;128(4):740-52.) and Manheimer(³⁶36 Mannheimer PD. The light-tissue interaction of pulse oximetry. Anesth Analg. 2007;105(6 Suppl):S10-7.)
Skin color	Occult hypoxemia (an arterial oxygen saturation of < 88% despite an oxygen saturation of 92 to 96% on pulse oximetry) was more common in Black (11.7%; 95%CI, 8.5 to 16.0) compared to White patients (3.6%; 95%CI, 2.7 to 4.7)	Sjöberg et al.(³⁵35 Sjöberg F, Singer M. The medical use of oxygen: a time for critical reappraisal. J Intern Med. 2013;274(6):505-28.)

Reference	Sample size (observations)	Population	Disease	Intervention (MV, NIV or SB)	Comparison between S/F and P/F	Outcomes
Neonatal and pediatric clinical studies
Khemani et al.(⁶6 Khemani RG, Rubin S, Belani S, Leung D, Erickson S, Smith LS, et al. Pulse oximetry vs. PaO2 metrics in mechanically ventilated children: Berlin definition of ARDS and mortality risk. Intensive Care Med. 2015;41(1):94-102.)	1,201	Children within 7 days	NA	MV within 7 days in pediatric ICU	At D1, S/F better discriminated mortality than P/F (p = 0.0003)	S/F ≤ 150, mortality 38.3%; S/F = 150 - 221, mortality 6.0%; S/F = 221 - 265, mortality 1,5%; S/F > 265, mortality 2.6%
Thomas et al.(⁷7 Thomas NJ, Shaffer ML, Willson DF, Shih MC, Curley MA. Defining acute lung disease in children with the oxygenation saturation index. Pediatr Crit Care Med. 2010;11(1):12-7.)	255 (2,839 observations)	Children and adolescents < 21 years	ARDS	Instillation of calfactant or placebo and 102 prone versus supine	S/F ≤ 253 indicated P/F ≤ 300 with 93% sensitivity and 43% specificity S/F ≤ 212 indicated P/F ≤ 200 with 76% sensitivity and 83% specificity	NA
Khemani et al.(⁴⁸48 Khemani RG, Thomas NJ, Venkatachalam V, Scimeme JP, Berutti T, Schneider JB, Ross PA, Willson DF, Hall MW, Newth CJ; Pediatric Acute Lung Injury and Sepsis Network Investigators (PALISI). Comparison of SpO2 to PaO2 based markers of lung disease severity for children with acute lung injury. Crit Care Med. 2012;40(4):1309-16.)	137 (1,207 observations)	Children >27 weeks gestational age and < 18 years	Any that required MV	Controlled MV	1/S/F = 0.00232 + 0.443/P/F S/F = 221 (95%CI 215 - 226) indicating P/F = 200, with 88% sensitivity and 78% specificity in detecting P/F < 200 S/F = 264 (95%CI 259 - 269) indicating P/F = 300, with 91% sensitivity and 53% specificity in detecting P/F < 300	NA
Lobete Prieto et al.(⁴⁹49 Lobete Prieto C, Medina Villanueva A, Modesto I Alapont V, Rey Galán C, Mayordomo Colunga J, los Arcos Solas M. [Prediction of PaO2/FiO2 ratio from SpO2/FiO2 ratio adjusted by transcutaneous CO2 measurement in critically ill children]. An Pediatr (Barc). 2011;74(2):91-6. Spanish.)	8 (40 observations)	Children admitted to ICU (age = 4.62 years)	Any that required intensive care	NA	S/F = 256.7 indicating P/F < 200 with 84,6% sensitivity and 85,2% specificity S/F = 297.6 indicating P/F < 300 with 89.7% sensitivity and 82% specificity	NA
Lobete et al.(⁵⁰50 Lobete C, Medina A, Rey C, Mayordomo-Colunga J, Concha A, Menéndez S. Correlation of oxygen saturation as measured by pulse oximetry/fraction of inspired oxygen ratio with Pao2/fraction of inspired oxygen ratio in a heterogeneous sample of critically ill children. J Crit Care. 2013;28(4):538. e1-7.)	235 (1,643 observations)	Children admitted to ICU	Any that required intensive care (except cardiac surgery)	MV, NIV and SB	1/S/F = 0.00164 + 0.521/P/F (p < 0.0001, R² = 0.843) S/F = 296 (95%CI 285 - 308) indicated P/F < 300, with 91% sensitivity and 87% specificity S/F = 236 (95%CI 228 - 244) indicated P/F < 200, with 88% sensitivity and 86% specificity S/F = 146 (95%CI 142-150) indicated P/F < 100, with 52% sensitivity and 99% specificity	NA
Bilan et al.(⁵¹51 Bilan N, Dastranji A, Ghalehgolab Behbahani A. Comparison of the SpO2/ FiO2 ratio and the PaO2/FiO2 ratio in patients with acute lung injury or acute respiratory distress syndrome. J Cardiovasc Thorac Res. 2015;7(1):28-31.)	70	Children admitted to ICU (age = 32 ± 5 months)	ARDS	MV	S/F = 235 indicated P/F < 300 with 57% sensitivity and 100% specificity S/F = 181 indicated P/F < 200 with 71% sensitivity and 82% specificity	NA
Wong et al.(⁵²52 Wong JJ, Loh TF, Testoni D, Yeo JG, Mok YH, Lee JH. Epidemiology of pediatric acute respiratory distress syndrome in Singapore: risk factors and predictive respiratory indices for mortality. Front Pediatr. 2014;2:78.)	70	Pediatric ICU patients (1 day to 16 years)	ARDS	MV, NIV and SB	NA	S/F at D3: survivors: 221; nonsurvivors: 149; p = 0.006 S/F at D7: survivors: 277; nonsurvivors: 146; p = 0,002
No ARDS clinical studies
Bass et al.(²2 Bass CM, Sajed DR, Adedipe AA, West TE. Pulmonary ultrasound and pulse oximetry versus chest radiography and arterial blood gas analysis for the diagnosis of acute respiratory distress syndrome: a pilot study. Crit Care. 2015;19(1):282.)	77	Clinical stable adult patients under MV	Any that required MV	MV with PEEP ≥ 5cmH2O	Spearman r = 0.83; p < 0.0001 S/F ≤ 315 indicated P/F ≤ 3 00 with 83% sensitivity and 50% specificity and S/F ≤ 235 indicated P/F ≤ 200 with 70% sensitivity and 90% specificity = 90%	NA
Venegas Sosa et al.(³3 Venegas Sosa AM, Cortés Munguía JA, Flores López EN, Colín Rodríguez J. Correlación de SpO2/FiO2 versus PaO2/FiO2 para monitoreo de la oxigenación en pacientes con trauma de tórax. Med Crit (Col Mex Med Crit). 2018;32(4):201-7.)	25	Adults (mean age = 37 years)	Thoracic trauma	MV	Pearson r (all with p < 0.05) At admission: r = 0.616 7 hours from admission: r = 0.68 14 hours from admission: r = 0.86 24 hours from admission: r = 0.89 31 hours from admission: r = 0.92 38 hours from admission: r = 0.90 48 hours from admission: r = 0.91	NA
Zeserson et al.(⁸8 Zeserson E, Goodgame B, Hess JD, Schultz K, Hoon C, Lamb K, et al. Correlation of venous blood gas and pulse oximetry with arterial blood gas in the undifferentiated critically ill patient. J. Intensive Care Med. 2018;33(3):176-81.)	129	Adults	Any emergency department patient	MV, NIV or SB	SpO2 ≥ 90% correlated with a PaO2 ≥ 60mmHg	NA
Namendys- Silva et al.(11)	232	ICU patients ≥16 years	Any that required ICU	MV	Used Pandharipande et al.(¹⁰10 Pandharipande PP, Shintani AK, Hagerman HE, St Jacques PJ, Rice TW, Sanders NW, et al. Derivation and validation of Spo2/Fio2 ratio to impute for Pao2/Fio2 ratio in the respiratory component of the Sequential Organ Failure Assessment score. Crit Care Med. 2009;37(4):1317-21.) for substituing P/F for S/F: S/F ≤ 512 indicating P/F ≤ 400 S/F ≤ 357 indicating P/F ≤ 300 S/F ≤ 214 indicating P/F ≤ 200 S/F ≤ 89 indicating P/F ≤ 100	Higher S/F ratio for survivors than for nonsurvivors at admission and at 48 hours of admission
Schmidt et al.(⁵³53 Schmidt MF, Gernand J, Kakarala R. The use of the pulse oximetric saturation to fraction of inspired oxygen ratio in an automated acute respiratory distress syndrome screening tool. J Crit Care. 2015;30(3):486-90.)	3,767 (7,544 observations)	Adults ≥ 18 years	Any that required MV	MV	Spearman r = 0.95 and correlation coefficient = 0.72 between S/F and P/F Log10 (P/F ratio) = 1.07*Log10 (S/F ratio) - 0.15 No impact after PEEP inclusion S/F = 295 indicated P/F ≤ 300 with 99% sensitivity and 9.9% specificity	NA
Kwack et al.(⁵⁴54 Kwack WG, Lee DS, Min H, Choi YY, Yun M, Kim Y, et al. Evaluation of the SpO2/FiO2 ratio as a predictor of intensive care unit transfers in respiratory ward patients for whom the rapid response system has been activated. PLoS One. 2018;13(7):e0201632.)	456	Adults (median age = 75 years)	NA	NA	NA	Lower S/F in patients transferred from general ward to ICU (medians 165 versus 320, p < 0.01) and in mortality versus survival groups (medians 217 versus 307, p < 0.01)
Sanz et al.(⁵⁵55 Sanz F, Dean N, Dickerson J, Jones B, Knox D, Fernández-Fabrellas E, et al. Accuracy of PaO2/FiO2 calculated from SpO2 for severity assessment in ED patients with pneumonia. Respirology. 2015;20(5):813-8.)	Valencian cohort: 926 Utah cohort: 213	Adults in Valencian cohort (73 years) Utah cohort (67 years)	Pneumonia	NA	Agreement when P/F < 200: (Ellis)(⁵⁶56 Ellis RK. Determination of PO2 from saturation. J Appl Physiol. 1989;67(2):902.) - 92%; (Rice et al.)(⁴4 Rice TW, Wheeler AP, Bernard GR, Hayden DL, Schoenfeld DA, Ware LB; National Institutes of Health, National Heart, Lung, and Blood Institute ARDS Network. Comparison of the SpO2/FIO2 ratio and the PaO2/FIO2 ratio in patients with acute lung injury or ARDS. Chest. 2007;132(2):410-7.) - 91% Agreement when P/F < 300: (Ellis)(⁵⁶56 Ellis RK. Determination of PO2 from saturation. J Appl Physiol. 1989;67(2):902.) - 80%; (Rice et al.)(⁴4 Rice TW, Wheeler AP, Bernard GR, Hayden DL, Schoenfeld DA, Ware LB; National Institutes of Health, National Heart, Lung, and Blood Institute ARDS Network. Comparison of the SpO2/FIO2 ratio and the PaO2/FIO2 ratio in patients with acute lung injury or ARDS. Chest. 2007;132(2):410-7.) - 70%	NA
Tripathi et al.(⁵⁷57 Tripathi RS, Blum JM, Rosenberg AL, Tremper KK. Pulse oximetry saturation to fraction inspired oxygen ratio as a measure of hypoxia under general anesthesia and the influence of positive end-expiratory pressure. J Crit Care. 2010;25(3):542.e9-13.)	2,754 (4,439 observations)	Adults ≥18 years	General anesthesia (nonthoracic and noncardiac)	MV with PEEP	Correlation between P/F and S/F: r = 0.46, p < 0.01) significant in any PEEP Linear regression: S/F = (0.26 x P/F) + 128 S/F = 206 indicated P/F = 300 S/F = 180 indicated P/F = 200	NA
Serpa Neto et al.(⁵⁸58 Serpa Neto A, Cardoso SO, Ong DS, Espósito DC, Pereira VG, Manetta JA, et al. The use of the pulse oximetric saturation/fraction of inspired oxygen ratio for risk stratification of patients with severe sepsis and septic shock. J Crit Care. 2013;28(5):681-6.)	260	Adults≥18 years (mean age=63 years)	Sepsis	NA	S/F ratio = 132.27 + 0.30 × (P/F) (p < 0.0001; r = 0.487) S/F = 154 indicated P/F = 100 S/F = 241 indicated P/F = 300	HR for death according to cutoff: S/F 241 - 192: HR = 1.70 (0.77 - 3.78) S/F 192 - 154: HR = 1.64 (0.66 - 4.08) S/F < 154: HR = 2.05 (1.11 - 3.81)
Mantilla et al.(⁵⁹59 Mantilla BM, Ramírez CA, Valbuena S, Muñoz L, Hincapié GA, Bastidas AR. [Oxygen saturation/fraction of inspired oxygen as a predictor of mortality in patients with exacerbation of COPD treated at the Central Military Hospital]. Acta Med Colomb. 2017;42(4):215-23. Spanish.)	462	Adults	Exacerbated COPD	MV, NIV and SB	NA	78.6% sensitivity and 39.2% specificity for S/F in predicting mortality
Adams et al.(⁶⁰60 Adams JY, Rogers AJ, Schuler A, Marelich GP, Fresco JM, Taylor SL, et al. Association between peripheral blood oxygen saturation (SpO2)/ fraction of inspired oxygen (FiO2) ratio time at risk and hospital mortality in mechanically ventilated patients. Perm J. 2020;24:19.)	25,944 (3,505,707 observations)	Adult nonparturient (mean age 65 years)	Any that required MV	MV	S/F and P/F showed moderate (r = 0.47) correlation for measures available in same hour and strong (r = 0.68) correlation when restricted to P/F < 400 and SpO2 ≤ 96%	Proportion of time with S/F < 150 (S/F-TAR) associated with higher mortality in the first 24 hours of MV In the first 24 hours of MV: S/F-TAR 0% = 16.4% mortality S/F-TAR 91 - 100% = 70.2% mortality Each 10% increase in S/F-TAR associated with 24% increase in hospital mortality (OR = 1.24 [95%CI 1.23 - 1.26], p < 0.001)
ARDS clinical studies
Rice et al.(⁴4 Rice TW, Wheeler AP, Bernard GR, Hayden DL, Schoenfeld DA, Ware LB; National Institutes of Health, National Heart, Lung, and Blood Institute ARDS Network. Comparison of the SpO2/FIO2 ratio and the PaO2/FIO2 ratio in patients with acute lung injury or ARDS. Chest. 2007;132(2):410-7.)	672 for derivation (2,673 observations) and 402 for validation (2,031 observations)	ARDS network trial patients: Derivation: Low VT group Validation: High PEEP versus Low PEEP groups	ARDS	MV (Low VT and high versus low PEEP)	Spearman r = 0.89; p < 0.0001 S/F = 64 + 0.84 x (P/F) Effect of PEEP on S/F ratio (p < 0.001): S/F = 129 + 0.72 x (P/F) - 4.0 x (PEEP) - 0.008 x (PEEP) x (P/F) S/F = 235 indicated P/F = 200 and S/F = 315 indicated P/F = 300	NA
Pandharipande et al.(¹⁰10 Pandharipande PP, Shintani AK, Hagerman HE, St Jacques PJ, Rice TW, Sanders NW, et al. Derivation and validation of Spo2/Fio2 ratio to impute for Pao2/Fio2 ratio in the respiratory component of the Sequential Organ Failure Assessment score. Crit Care Med. 2009;37(4):1317-21.)	4728 Group 1 - 1,742 observations Group 2 - 2,986 observations, only for SpO2 ≤ 98%	Group 1 - Adults under general anesthesia for noncardiovascular or thoracic surgeries Group 2 - ARDS network trial patients: Low versus High VT	Group 1 - any surgical patient Group 2 - ARDS	MV	Spearman’s rho (p < 0,001) for SOFA with S/F and P/F: overall = 0.85 Group 1 Log (P/F)=0.48+0.78xLog(S/F) Group 2 PEEP < 8cmH2O; Log (P/F) = 0.06 + 0.94 x Log (S/F) PEEP 8 - 12cmH2O Log (P/F) =-0.13+1.01 x Log (S/F) PEEP > 12cmH2O Log (P/F) =-0.47 + 1.17 x Log (S/F)	Similar correlations between SOFA scores using P/F and S/F for ICU LOS and VFD ICU LOS versus SOFA respiratory using S/F: r = 0.36 (p = 0.013) VFD versus SOFA respiratory using S/F: r =-0.33 (p = 0.025)
Brown et al.(61)	1,184	ARDS network (EDEN, OMEGA and SAILS) trial patients	ARDS	NA	Correlation between measured and imputed P/F using S/F from: (Ellis)(⁵⁶56 Ellis RK. Determination of PO2 from saturation. J Appl Physiol. 1989;67(2):902.), nonlinear: r = 0.84 (Rice et al.)(⁴4 Rice TW, Wheeler AP, Bernard GR, Hayden DL, Schoenfeld DA, Ware LB; National Institutes of Health, National Heart, Lung, and Blood Institute ARDS Network. Comparison of the SpO2/FIO2 ratio and the PaO2/FIO2 ratio in patients with acute lung injury or ARDS. Chest. 2007;132(2):410-7.) linear: r = 0.733 (Pandharipande et al.)(¹⁰10 Pandharipande PP, Shintani AK, Hagerman HE, St Jacques PJ, Rice TW, Sanders NW, et al. Derivation and validation of Spo2/Fio2 ratio to impute for Pao2/Fio2 ratio in the respiratory component of the Sequential Organ Failure Assessment score. Crit Care Med. 2009;37(4):1317-21.) log-linear: r = 0.73	NA
Chen et al.(62)	101	ICU patients (mean age 69 years)	ARDS	MV	NA	Lowest S/F ratio during ICU stay (148 in survivors versus 139 in nonsurvivors) associated with mortality (p=0.046) AUC for S/F (0.616, p = 0.046) for mortality prediction AUC from P/F (0.603; p = 0.08) for mortality prediction
Chen et al.(⁶³63 Chen W, Janz DR, Shaver CM, Bernard GR, Bastarache JA, Ware LB. Clinical characteristics and outcomes are similar in ARDS diagnosed by oxygen saturation/Fio2 ratio compared with Pao2/Fio2 ratio. Chest. 2015;148(6):1477-83.)	124	ICU patients ≥ 18 years	ARDS	NA	Used predefined cutoff of S/F < 315 for ARDS. Overall discordance between S/F and P/F for ARDS diagnosis was 8.2% (n = 30 from 362)	S/F cutoffs for ARDS severity and mortality rates: 315 - mild: 30.6% 235 - moderate: 23.1% 144 - severe: 61.1% p < 0.001
Covid-19 clinical studies
Lu et al.(¹²12 Lu X, Jiang L, Chen T, Wang Y, Zhang B, Hong Y, et al. Continuously available ratio of SpO2/FiO2 serves as a noninvasive prognostic marker for intensive care patients with COVID-19. Respir Res. 2020;21(1):194.)	280	Severe and critically ill COVID-19 patients	COVID-19	MV, NIV and SB	NA	Strong association between √S/F and the risk for death, corresponding to 1.82-fold increase (95%CI: 1.56-2.13) in the mortality risk
Wang et al.(⁶⁴64 Wang Y, Lu X, Li Y, Chen H, Chen T, Su N, et al. Clinical course and outcomes of 344 intensive care patients with COVID-19. Am J Respir Crit Care Med. 2020;201(11):1430-4.)	344	Severe and critically ill COVID-19 patients	COVID-19	MV, NIV and SB	NA	Negative correlation between S/F ratio and ARDS incidence (r =-0.68) - every 10 units increase in S/F correlated with 10% decrease in fatality (HR = 0.90; p < 0.001)

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[1] Conflicts of interest: None.