What is the optimal target for oxygen saturation (SpO2) in patients with acute hypoxemic respiratory failure?

The optimal target for oxygen saturation (SpO2) in patients with acute hypoxemic respiratory failure is unknown. Hypoxemia causes pulmonary vasoconstriction and pulmonary hypertension in its chronic form, and death when it is acute and severe. Hyperoxemia also causes physiologic disturbances, through toxic reactive oxygen species and absorption atelectasis.1

The World Health Organization (WHO) interim guidance for patients with hypoxemic respiratory failure due to COVID-19 suggests an initial SpO2 target >94% for stabilization, then >90% for non-pregnant patients and 92-95% for pregnant patients, once stable.2 The summary of evidence below suggests another reasonable target might be SpO2 90-96%, and perhaps 92-96% in settings with only intermittent pulse oximetry monitoring, or in patients with darker skin pigmentation.

The evidence

Several recent studies have examined conservative versus liberal oxygenation targets, with mixed results (See Table). In 2016, a before and after stepwise implementation study found a trend toward improved clinical outcomes with SpO2 target of 92-95% and PaO2 target of 55-86 mmHg as compared with earlier higher targets in ICU patients.3 Also in 2016, a single-center, open-label, randomized clinical trial compared targets of SpO2 94-98%/paO2 70-100 mmHg versus SpO2 97-100%/paO2 up to 150 mmHg in ICU patients, and found a mortality benefit with the lower target; however, the study was stopped early due to poor enrollment after a natural disaster, so its results cannot be considered definitive.4

In 2020, two multicenter randomized trials published together in the New England Journal of Medicine produced different results. One compared targets of SpO2 88-92%/paO2 55-70 mmHg with SpO2>=96%/PaO2 90-105 mmHg in ARDS patients, and was stopped early for suggestion of harm in the lower-SpO2 target arm.5 The other compared one arm with a target SpO2<97% with an arm with no maximum target SpO2 limit (lower limit 90% for both arms) in mechanically ventilated patients, and found no difference in ventilator-free days or 180-day mortality.6

Finally, in a 2021 multicenter randomized trial also in the New England Journal of Medicine, investigators randomized almost 3,000 ICU patients with acute hypoxemic respiratory failure to receive PaO2 targets of either 60 mmHg or 90 mmHg.7 The median SpO2 in the higher-target group was 96% (IQR 95-97%), and in the lower-target group was 93% (IQR 92-94%). The study found no difference in 90-day mortality.

The evidence taken together suggests that a target range that avoids both hypoxemia and hyperoxemia may be beneficial. A reasonable example target range based on the above evidence is SpO2 of 90-96%.

Other considerations

Other factors may need to be considered when deciding on a Spo2 target range:

1) Resource-variable settings:

• Lower target saturations can conserve scarce oxygen resources, making more oxygen available for more patients who need it; a hospital Emergency Department in Rwanda found that a target of 90-95% resulted in better oxygen supply reserves for the hospital, as compared with previous higher SpO2 targets.8
• Intermittent pulse oximetry monitoring (versus continuous) could increase the risk for periods of undetected hypoxemia.1 This could be an argument for a slightly higher target, for example 92-96%.
• The accuracy of inexpensive pulse oximeters without regulatory approval is variable.9 Using validated oximeters and following trends in SpO2 rather than individual measurements, and/or checking saturations with more than one device, may help mitigate this concern.

2) Race and skin pigmentation: Data suggest that pulse oximetry more frequently under reports hypoxemia in patients who self-identify as Black, as compared with patients who self-identify as White.10 While more work needs to be done with specific devices and with documentation of a validated range of skin pigmentations, it may be reasonable currently to target higher ranges in patients with darker skin tones, for instance 93-96%. 

3) Altitude: Geographic variation in elevation above sea level may necessitate adjustment in SpO2 targets. Baseline SpO2 values in healthy people will be lower at higher elevation due to decreases in the partial pressure of oxygen.

 4) Other conditions: The recommendations here are related to acute hypoxemic respiratory failure. Other conditions may necessitate higher or lower targets. For example, a COPD exacerbation in a patient with chronic hypercarbic respiratory failure should likely have a lower target of 88% to avoid worsening of hypercarbia. Pregnant patients generally have higher SpO2 goals.2 

Citations

1.     Angus DC. Oxygen Therapy for the Critically Ill. N Engl J Med 2020;382:1054-6.
2.     World Health Organization. Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected: Interim guidance. 2020 March 13.
3.     Helmerhorst HJ, Schultz MJ, van der Voort PH, Bosman RJ, Juffermans NP, de Wilde RB, van den Akker-van Marle ME, van Bodegom-Vos L, de Vries M, Eslami S, de Keizer NF, Abu-Hanna A, van Westerloo DJ, de Jonge E. Effectiveness and Clinical Outcomes of a Two-Step Implementation of Conservative Oxygenation Targets in Critically Ill Patients: A Before and After Trial. Crit Care Med 2016;44:554-63.
4.     Girardis M, Busani S, Damiani E, Donati A, Rinaldi L, Marudi A, Morelli A, Antonelli M, Singer M. Effect of Conservative vs Conventional Oxygen Therapy on Mortality Among Patients in an Intensive Care Unit: The Oxygen-ICU Randomized Clinical Trial. Jama 2016;316:1583-9.
5.     Barrot L, Asfar P, Mauny F, Winiszewski H, Montini F, Badie J, Quenot JP, Pili-Floury S, Bouhemad B, Louis G, Souweine B, Collange O, Pottecher J, Levy B, Puyraveau M, Vettoretti L, Constantin JM, Capellier G. Liberal or Conservative Oxygen Therapy for Acute Respiratory Distress Syndrome. N Engl J Med 2020;382:999-1008.
6.     Mackle D, Bellomo R, Bailey M, Beasley R, Deane A, Eastwood G, Finfer S, Freebairn R, King V, Linke N, Litton E, McArthur C, McGuinness S, Panwar R, Young P. Conservative Oxygen Therapy during Mechanical Ventilation in the ICU. N Engl J Med 2020;382:989-98.
7.     Schjørring OL, Klitgaard TL, Perner A, Wetterslev J, Lange T, Siegemund M, Bäcklund M, Keus F, Laake JH, Morgan M, Thormar KM, Rosborg SA, Bisgaard J, Erntgaard AES, Lynnerup AH, Pedersen RL, Crescioli E, Gielstrup TC, Behzadi MT, Poulsen LM, Estrup S, Laigaard JP, Andersen C, Mortensen CB, Brand BA, White J, Jarnvig IL, Møller MH, Quist L, Bestle MH, Schønemann-Lund M, Kamper MK, Hindborg M, Hollinger A, Gebhard CE, Zellweger N, Meyhoff CS, Hjort M, Bech LK, Grøfte T, Bundgaard H, Østergaard LHM, Thyø MA, Hildebrandt T, Uslu B, Sølling CG, Møller-Nielsen N, Brøchner AC, Borup M, Okkonen M, Dieperink W, Pedersen UG, Andreasen AS, Buus L, Aslam TN, Winding RR, Schefold JC, Thorup SB, Iversen SA, Engstrøm J, Kjær MN, Rasmussen BS. Lower or Higher Oxygenation Targets for Acute Hypoxemic Respiratory Failure. N Engl J Med 2021.
8.     Sutherland T, Moriau V, Niyonzima JM, Mueller A, Kabeja L, Twagirumugabe T, Rosenberg N, Umuhire OF, Talmor DS, Riviello ED. The “Just Right” Amount of Oxygen. Improving Oxygen Use in a Rwandan Emergency Department. Ann Am Thorac Soc 2019;16:1138-42.
9.     Lipnick MS, Feiner JR, Au P, Bernstein M, Bickler PE. The Accuracy of 6 Inexpensive Pulse Oximeters Not Cleared by the Food and Drug Administration: The Possible Global Public Health Implications. Anesth Analg 2016;123:338-45.
10.     Sjoding MW, Dickson RP, Iwashyna TJ, Gay SE, Valley TS. Racial Bias in Pulse Oximetry Measurement. N Engl J Med 2020;383:2477-8.