# Hypoxemia laboratory findings

 Hypoxemia Microchapters

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

## Overview

Laboratory findings consistent with the diagnosis of [hypoxemia] are listed below].

## Laboratory Findings

### Shunting

#### PaO2/FiO2 ratio

Severity of ARDS[1]
Severity PaO2/FiO2
Mild <300
Moderate <200
Severe <100

The PaO2/FiO2 ratio (PF ratio) is also called the Carrico index.

Ratio = PaO2/FiO2

An example in a healthy person:

Ratio = PaO2/0.21

${P/F\ ratio} = \left (\frac{PaO_2}{Fi0_2}\right) \times 100$

An example in a healthy person:

${476} = \left (\frac{100\ mm\ Hg}{21%}\right) \times 100$

A higher ratio indicates better gas exchange:

• Normal is 500
• ARDS suggested by < 300[1]

Interpretation is complicated by the ratio varying with FiO2[2].

Comparative studies suggest this measure correlates better with pulmonary shunts than does the A-a gradient.[3][4][5]

As compared to the SF ratio, this requires arterial blood to measure.

#### SpO2/FiO2 ratio

Correlation of PaO2/FiO2 and SpO22/FiO2[6]
SOFA Respiratory score PaO2/FiO2 SpO22/FiO2
1 <400 <512
2 <300 <357
3 <200 <214
4 <100 <89

The SpO2/FiO2 ratio (SF ratio) is the ratio of oxyhemoglobin saturation measured by pulse oximetry (SpO2) to FiO. The ratio correlates with the PaO2/FiO2 ratio (R = 0.89; 'strong') although the correlation becomes non-linear at values below 300 when hypoxic[7]. A ratio of 315 predicts a PaO2/FiO2 of 300[8].

The accuracy of a ratio < 315 for detecting a PF ratio of < 300 is:

• Sensitivity 91% and specificity 56%[8]
• Sensitivity 83% and specificity 50%[9]

However, the accuracy varies with PEEP[6]

Clinical interpretation

• > 452 suggests normal based on an oxygen saturation of 95% being considered normal.
• < 443 suggests need for oxygen therapy based on the recommendation that supplemental oxygen be administered to a spontaneously breathing patient with O2sat < 93%[10]
• < 421 is associated with mortality among patients with sepsis[11].
• < 315 suggest ARDS[8][9] and a value of < 300 suggests need to transfer to intensive care[12].
• A change of 14 in the SF ratio is meaningful based on the standard deviation of the SF ratio reported as 69[8] and a 'small' statistical change being 0.2 times that standard deviation[13]. The SF ratio has been tracked over time to monitor H1N1 infection[14]

#### AVO2D

The alveolar-arterial oxygen (A-a) difference (AVO2D) or A-a gradient

$\mbox{A-a gradient} = {PAO_2}\ -\ {PaO_2}$
${PAO_2} = {Fi0_2} *\left ({760 - 47}\right) \ -\ \frac{PaCO_2}{0.8}$
• Normal is < 10 mm Hg or 2.5 + 0.21 x age in years[15]

The A-a gradient is harder to calculate, but accounts for changes in respiration as measured by the partial pressure of carbon dioxide. However, this calculation relies on the respiratory quotient being constant in the prediction of alveolar CO2.

When compared to the PF ratio, the A-a gradient is found to correlate less well with pulmonary shunting.[3][4][5]

Among outpatients with possible pulmonary embolism, the A-a gradient may be a better test than oxygen saturation.[16]

A change of 14 in the SF ratio is meaningful based on the standard deviation of the SF ratio reported as 68[8] and a 'small' statistical change being 0.2 times that standard deviation[13]

#### Oxygenation index

The oxygenation index is the (mean airway pressure×FiO2×100)÷PaO2[17]. The oxygenation index may be predict mortality than the PF ratio[17].

### Tissue perfusion

Central venous oxygen saturation (ScvO2)

In patients with septic shock, maintaining the central venous oxygen saturation (ScvO2) > 70% is a health care quality assurance measure for the Institute for Healthcare Improvement.[18] This is measured from the superior vena cava. This is hard to predict by physical examination.[19]

Mixed venous oxygen saturation (SvO2)

In patients with septic shock, maintaining the mixed venous oxygen saturation (ScvO2) > 65% is a health care quality assurance measure for the Institute for Healthcare Improvement that is an alternative to the central venous oxygen saturation.[20] This is measured from a pulmonary artery catheter. This is hard to predict by physical examination.[19]

The mixed venous pressure may be lower than the central venous pressure due to mixing with blood from the splanchnic circulation or carotid sinuses that has lower oxygen content.[21]

Tissue oxygen saturation (StO2)

Tissue oxygen saturation (StO2) at the thenar eminence may be an alternative, non-invasive measurement.[22][23]

Lactate clearance

Maintaining lactate clearance about 10% may be an easier alternative than invasive measurements of oxygenation according to a randomized controlled trial by EMShockNet.[24]

Capnography

Capnography, which is "continuous recording of the carbon dioxide content of expired air,"[25] may detect respiratory depression before hypoxemia occurs.[26] Proposed criteria for respiratory depression are:[26]

• End tidal CO2 (ETCO2) level 50 mm Hg
• ETCO2 change from baseline of 10%
• Loss of waveform for 15 seconds

## References

1. ARDS Definition Task Force. Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E; et al. (2012). "Acute respiratory distress syndrome: the Berlin Definition". JAMA. 307 (23): 2526–33. doi:10.1001/jama.2012.5669. PMID 22797452.
2. Karbing DS, Kjaergaard S, Smith BW, Espersen K, Allerød C, Andreassen S; et al. (2007). "Variation in the PaO2/FiO2 ratio with FiO2: mathematical and experimental description, and clinical relevance". Crit Care. 11 (6): R118. doi:10.1186/cc6174. PMC 2246207. PMID 17988390.
3. Covelli HD, Nessan VJ, Tuttle WK (1983). "Oxygen derived variables in acute respiratory failure". Crit. Care Med. 11 (8): 646–9. PMID 6409506.
4. El-Khatib MF, Jamaleddine GW (2004). "A new oxygenation index for reflecting intrapulmonary shunting in patients undergoing open-heart surgery". Chest. 125 (2): 592–6. PMID 14769743.
5. Cane RD, Shapiro BA, Templin R, Walther K (1988). "Unreliability of oxygen tension-based indices in reflecting intrapulmonary shunting in critically ill patients". Crit. Care Med. 16 (12): 1243–5. PMID 3191742.
6. Pandharipande PP, Shintani AK, Hagerman HE, St Jacques PJ, Rice TW, Sanders NW; et al. (2009). "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. 37 (4): 1317–21. doi:10.1097/CCM.0b013e31819cefa9. PMC 3776410. PMID 19242333.
7. Brown SM, Duggal A, Hou PC, Tidswell M, Khan A, Exline M; et al. (2017). "Nonlinear Imputation of PaO2/FIO2 From SpO2/FIO2 Among Mechanically Ventilated Patients in the ICU: A Prospective, Observational Study". Crit Care Med. 45 (8): 1317–1324. doi:10.1097/CCM.0000000000002514. PMC 5511089. PMID 28538439.
8. Rice TW, Wheeler AP, Bernard GR, Hayden DL, Schoenfeld DA, Ware LB; et al. (2007). "Comparison of the SpO2/FIO2 ratio and the PaO2/FIO2 ratio in patients with acute lung injury or ARDS". Chest. 132 (2): 410–7. doi:10.1378/chest.07-0617. PMID 17573487.
9. Bass CM, Sajed DR, Adedipe AA, West TE (2015). "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. 19: 282. doi:10.1186/s13054-015-0995-5. PMC 4511255. PMID 26325623.
10. Siemieniuk RAC, Chu DK, Kim LH, Güell-Rous MR, Alhazzani W, Soccal PM; et al. (2018). "Oxygen therapy for acutely ill medical patients: a clinical practice guideline". BMJ. 363: k4169. doi:10.1136/bmj.k4169. PMID 30355567.
11. Capan M, Hoover S, Ivy JS, Miller KE, Arnold R, S.E.P.S.I.S (Sepsis Early Prediction Support Implementation System) Collaborative (2018). "Not all organ dysfunctions are created equal - Prevalence and mortality in sepsis". J Crit Care. 48: 257–262. doi:10.1016/j.jcrc.2018.08.021. PMID 30245367.
12. Kwack WG, Lee DS, Min H, Choi YY, Yun M, Kim Y; et al. (2018). "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. 13 (7): e0201632. doi:10.1371/journal.pone.0201632. PMC 6067747. PMID 30063769.
13. Cohen J (1992). "A power primer". Psychol Bull. 112 (1): 155–9. PMID 19565683.
14. Sahasrabhojney et a. SpO2/FiO2 ratio: a prognostic marker for influenza patients. International J Research in Medical Sciences 2015 doi:10.18203/2320-6012.ijrms20151451
15. Mellemgaard K (1966). "The alveolar-arterial oxygen difference: its size and components in normal man". Acta Physiol Scand. 67 (1): 10–20. doi:10.1111/j.1748-1716.1966.tb03281.x. PMID 5963295.
16. McFarlane MJ, Imperiale TF (1994). "Use of the alveolar-arterial oxygen gradient in the diagnosis of pulmonary embolism". Am. J. Med. 96 (1): 57–62. PMID 8304364.
17. Seeley E, McAuley DF, Eisner M, Miletin M, Matthay MA, Kallet RH (2008). "Predictors of mortality in acute lung injury during the era of lung protective ventilation". Thorax. 63 (11): 994–8. doi:10.1136/thx.2007.093658. PMC 2771451. PMID 18566110.
18. Maintain Adequate Central Venous Oxygen Saturation Institute for Healthcare Improvement
19. Grissom CK, Morris AH, Lanken PN, Ancukiewicz M, Orme JF, Schoenfeld DA; et al. (2009). "Association of physical examination with pulmonary artery catheter parameters in acute lung injury". Crit Care Med. 37 (10): 2720–6. PMID 19885995.
20. Maintain Adequate Central Venous Oxygen Saturation Institute for Healthcare Improvement
21. Kopterides P, Mavrou I, Kostadima E (2005). "Central or mixed venous oxygen saturation?". Chest. 128 (2): 1073–4, author reply 1074-5. doi:10.1378/chest.128.2.1073. PMID 16100219.
22. Podbregar M, Mozina H (2007). "Skeletal muscle oxygen saturation does not estimate mixed venous oxygen saturation in patients with severe left heart failure and additional severe sepsis or septic shock". Crit Care. 11 (1): R6. doi:10.1186/cc5153. PMC 2147710. PMID 17227587.
23. Leone M, Blidi S, Antonini F, Meyssignac B, Bordon S, Garcin F; et al. (2009). "Oxygen tissue saturation is lower in nonsurvivors than in survivors after early resuscitation of septic shock". Anesthesiology. 111 (2): 366–71. doi:10.1097/ALN.0b013e3181aae72d. PMID 19602965.
24. Jones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA, Kline JA; et al. (2010). "Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial". JAMA. 303 (8): 739–46. doi:10.1001/jama.2010.158. PMID 20179283.
25. Anonymous (2024), Capnography (English). Medical Subject Headings. U.S. National Library of Medicine.
26. Deitch K, Miner J, Chudnofsky CR, Dominici P, Latta D (2010). "Does end tidal CO2 monitoring during emergency department procedural sedation and analgesia with propofol decrease the incidence of hypoxic events? A randomized, controlled trial". Ann Emerg Med. 55 (3): 258–64. doi:10.1016/j.annemergmed.2009.07.030. PMID 19783324.