Peripheral arterial oxygen saturation to fraction of inspired oxygen ratio: a versatile parameter for critically ill patients

Acute hypoxemic respiratory failure (AHRF) is a highly prevalent condition in critically ill patients. Regardless of the different causes leading to AHRF, a cornerstone diagnostic tool is calculating PaO₂/FiO₂ from arterial blood gas analysis. Nevertheless, PaO₂/FiO₂ has several practical limitations: arterial puncture is a painful procedure¹ that is technically challenging in some patients, and blood gas analyzers might not be widely available in prehospital care and hospitals in low-income and lower-middle-income countries. Because of these limitations, several authors have proposed the replacement of PaO₂/FiO₂ with SpO₂/FiO₂ as a tool not only for hypoxemia diagnosis but also for monitoring and determining prognosis.²-⁷Pulse oximeters are a low-cost, noninvasive technology widely used in healthcare. They determine oxygen saturation by measuring the light absorption of arterial blood at two specific wavelengths, namely, 660nm (red) and 940nm (infrared). The relative absorption at these two wavelengths, calibrated against direct measurements of SaO₂, generates the pulse-estimated SpO₂.⁸Pulse oximetry is accurate in reflecting SaO₂ when its value is above 90%. However, the accuracy worsens when the SaO₂ is lower than 90%, systematically underestimating SaO₂ when it is 80% or less.⁹

The oxyhemoglobin dissociation curve, from which SpO₂ is derived, is based on a well-established physiological concept, and its comprehension is important to understand some limitations in adopting SpO₂ and SpO₂/FiO₂ as markers of PaO₂/FiO₂ in clinical practice. The oxyhemoglobin dissociation curve has a sigmoidal shape, with a flat upper portion (Figure 1). In this flat portion, significant changes in the PaO₂ produce only small changes in SpO_2, and the relationship between SpO₂ and PaO₂ dramatically decreases. Therefore, to use SpO₂/FiO₂ for AHRF diagnosis and monitoring, SpO₂ must be ≤ 97%.¹⁰ In contrast, measuring SpO₂/FiO₂ in room air may also be an issue since patients with AHRF may develop life-threatening hypoxemia, and SpO₂/FiO₂ may lack sensitivity for AHRF diagnosis.¹¹ Moreover, several factors can shift the oxyhemoglobin dissociation curve to the left or to the right, changing the correlations between SpO₂ and PaO₂. The impact of these possible shifts in the accuracy of SpO₂/FiO₂ has not yet been well established (Figure 1).

Figure 1
Oxyhemoglobin dissociation curve. In the flat portion of the curve (dashed line), changes in arterial oxygen partial pressure produce small or no changes in arterial oxygen saturation (when values are greater than 97%).

Since the first attempts to replace PaO₂/FiO₂ for SpO₂/FiO₂, the SpO₂/FiO₂ ratio has been shown to be a promising tool in different scenarios. First, it has good performance as a prognostic variable. A 2020 COVID-19 cohort revealed a strong association between SpO₂/FiO₂ and the risk of death.⁵ Similar results were obtained in AHRF patients in the intensive care unit (ICU),¹² even showing a better mortality prediction ability for SpO₂/FiO₂ than well-established clinical scores such as the SOFA, APACHE II, and SAPS II. Using artificial intelligence, researchers identified SpO₂/FiO₂ as an independent predictor of ICU (OR = 2.73) and day-28 survival (OR = 3.96).¹³ Second, it has been successfully used to monitor respiratory function and assess treatment efficacy; for example, preterm infants in whom surfactant treatment failed had lower SpO₂/FiO₂.¹⁴ Third, it has been used as a surrogate for PaO₂/FiO₂ in AHRF diagnosis and as an input for PaO₂/FiO₂ in clinical scores. A SpO₂/FiO₂ ratio threshold of 350 had a positive predictive value of 0.88 for a PaO₂/FiO₂ < 300, and a SpO₂/FiO₂ threshold of 470 had a negative predictive value of 0.89 for a PaO₂/FiO₂ < 400. In a study with 703 critically ill patients, nonlinear PaO₂/FiO₂ imputation from SpO₂/FiO₂ had 0.9 sensitivity and 0.67 specificity for a PaO₂/FiO₂ < 300.¹⁵ More recently, the New Global Definition for Acute Respiratory Distress Syndrome¹⁶ allowed the use of SpO₂/FiO₂ ≤ 315 (if SpO₂ ≤ 97%) as an alternative to PaO₂/FiO₂ ≤ 300mmHg for the diagnosis of the syndrome. SpO₂/FiO₂ can also be used for classifying acute respiratory distress syndrome as mild (235 < SpO₂/FiO₂ ≤ 315), moderate (148 < SpO₂/FiO₂ ≤ 235) or severe (SpO₂/FiO₂ ≤ 148).

SpO₂/FiO₂ still has some important limitations, other than those related to oxyhemoglobin dissociation curve characteristics, to directly replace PaO₂/FiO₂ in clinical practice. First, their relationship is not perfectly linear, although studies have found regression equations that can reasonably predict PaO₂/FiO₂ from SpO₂/FiO₂.⁴ Second, SpO₂ reading errors can occur due to hypoperfusion, hypothermia, malposition of the probe, racial differences,¹⁷ or motion artifacts. Third, several conditions may lead to falsely elevated readings (i.e., carboxyhemoglobin, methemoglobin, sulfhemoglobin, or skin pigment) or falsely low readings (i.e., severe anemia, sickle hemoglobin, methemoglobin, sulfhemoglobin, nail polish, or vital dyes).¹⁸ Finally, the SpO₂/FiO₂ ratio logically depends on the FiO₂ amount, which can be challenging to measure precisely in some scenarios, especially with conventional oxygen therapy, nasal cannulas, and face masks with or without reservoirs, although conversion tables are available (Table 1S - Supplementary Material). However, this limitation also occurs when PaO₂/FiO₂ is used.

Future clinical studies addressing SpO₂/FiO₂ should not only try to estimate PaO₂/FiO₂ on the basis of an equation but also attempt to establish cutoff values and prognostic values for SpO₂/FiO₂ under specific protocols for mechanically ventilated or spontaneous breathing patients, defining a priori an optimal FiO₂ range. Strategies such as the SpO₂/FiO₂ diagram,¹¹ constructed by decremental FiO₂ titration from 100% to 21%, could be tested in an attempt to increase the specificity and specificity values for AHRF diagnosis. Thus far, it may be too early to recommend SpO₂/FiO₂ as a perfect replacement for PaO₂/FiO₂, since strong evidence from prospective studies is still lacking. Nevertheless, it is not just a promising tool but rather an option for diagnosis, monitoring, and prognosis when arterial blood gas analysis is not readily available or when its risks outweigh its benefits.

REFERENCES

• ¹ Catoire P, Tellier E, de la Rivière C, Beauvieux MC, Valdenaire G, Galinski M, et al. Assessment of the SpO2/FiO2 ratio as a tool for hypoxemia screening in the emergency department. Am J Emerg Med. 2021;44:116-20.
• ² Cresi F, Maggiora E, Lista G, Dani C, Borgione SM, Spada E, Ferroglio M, Bertino E, Coscia A; ENTARES Study Group. Effect of nasal continuous positive airway pressure vs heated humidified high-flow nasal cannula on feeding intolerance in preterm infants with respiratory distress syndrome: the ENTARES randomized clinical trial. JAMA Netw Open. 2023;6(7):E2323052.
• ³ Seth S, Saha B, Saha AK, Mukherjee S, Hazra A. Nasal HFOV versus nasal IPPV as a post-extubation respiratory support in preterm infants-a randomised controlled trial. Eur J Pediatr. 2021;180(10):3151-60.
• ⁴ Ray S, Rogers L, Pagel C, Raman S, Peters MJ, Ramnarayan P. PaO2/FiO2 ratio derived from the SpO2/FiO02 ratio to improve mortality prediction using the Pediatric Index of Mortality-3 Score in transported intensive care admissions. Pediatr Crit Care Med. 2017;18(3):e131-6.
• ⁵ Lu X, Jiang L, Chen T, Wang Y, Zhang B, Hong Y, et al. Continuously available ratio of SpO(2)/FiO(2) serves as a noninvasive prognostic marker for intensive care patients with COVID-19. Respir Res. 2020;21(1):194.
• ⁶ Ganesan G, Ponniah S, Sundaram V, Marimuthu PK, Pitchaikannu V, Chandrasekaran M, et al. Whole lung irradiation as a novel treatment for COVID-19: final results of the prospective randomized trial (WINCOVID trial). Radiother Oncol. 2022;167:133-42.
• ⁷ Chandna A, Mahajan R, Gautam P, Mwandigha L, Gunasekaran K, Bhusan D, et al. Facilitating safe discharge through predicting disease progression in moderate coronavirus disease 2019 (COVID-19): a prospective cohort study to develop and validate a clinical prediction model in resource-limited settings. Clin Infect Dis. 2022;75(1):E368-79.
• ⁸ Wukitsch MW, Petterson MT, Tobler DR, Pologe JA. Pulse oximetry: analysis of theory, technology, and practice. J Clin Monit. 1988;4(4):290-301.
• ⁹ Jubran A. Pulse oximetry. Intensive Care Med. 2004;30(11):2017-20.
• ¹⁰ 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.
• ¹¹ Tusman G, Bohm SH, Suarez-Sipmann F. Advanced uses of pulse oximetry for monitoring mechanically ventilated patients. Anesth Analg. 2017;124(1):62-71.
• ¹² Fukuda Y, Tanaka A, Homma T, Kaneko K, Uno T, Fujiwara A, et al. Utility of SpO2/FiO2 ratio for acute hypoxemic respiratory failure with bilateral opacities in the ICU. PLoS One. 2021;16(1):e0245927.
• ¹³ Bodenes L, N'Guyen QT, Le Mao R, Ferrière N, Pateau V, Lellouche F, et al. Early heart rate variability evaluation enables to predict ICU patients' outcome. Sci Rep. 2022;12(1):2498.
• ¹⁴ Radicioni M, Pennoni S, Fantauzzi A, Bini V, Camerini P. Ultrasound evaluation of diaphragm kinetics after minimally invasive surfactant administration. J Ultrasound. 2024;27(1):87-96.
• ¹⁵ Brown SM, Duggal A, Hou PC, Tidswell M, Khan A, Exline M, Park PK, Schoenfeld DA, Liu M, Grissom CK, Moss M, Rice TW, Hough CL, Rivers E, Thompson BT, Brower RG; National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) Prevention and Early Treatment of Acute Lung Injury (PETAL) Network. Nonlinear imputation of PaO2/FIO2 from SpO2/FIO2 among mechanically ventilated patients in the ICU: a prospective, observational study. Crit Care Med. 2017;45(8):1317-24.
• ¹⁶ Matthay MA, Arabi Y, Arroliga AC, Bernard G, Bersten AD, Brochard LJ, et al. A new global definition of acute respiratory distress syndrome. Am J Respir Crit Care Med. 2024;209(1):37-47.
• ¹⁷ Sjoding MW, Dickson RP, Iwashyna TJ, Gay SE, Valley TS. Racial bias in pulse oximetry measurement. N Engl J Med. 2020;383(25):2477-8.
• ¹⁸ Ralston AC, Webb RK, Runciman WB. Potential errors in pulse oximetry: I. Pulse oximeter evaluation. Anaesthesia. 1991;46(3):202-6.

Edited by

• Responsible editor:
  Alexandre Biasi Cavalcanti

Publication Dates

• Publication in this collection
  27 Jan 2025
• Date of issue
  2025

History

• Received
  18 May 2024
• Accepted
  14 July 2024