1. Advances in Pulse Oximetry
Samuel Y. Ash, M.D.
Resident, Department of Internal Medicine
University of Washington Medical Center

2. Disclosures
No financial disclosures.
Research presented is unfunded.

3. Outline Background and Technological Review
Limitations of Traditional Pulse Oximetry
Next Generation Pulse Oximetry
Pulse CO-Oximetry
Applications of Pulse CO-Oximetry
Conclusions
Future Areas of Research

4. Background and Technological Review
Beer-Lambert Law:
by knowing the absorptive properties of a solution or tissue, one can determine the relative concentrations of the solutes in that solution or tissue

5. Background and Technological Review
Traditional Pulse Oximetry:
940nm
Near-infrared
Oxyhemoglobin
660nm
Red
Deoxyhemoglobin
Image source: Isenhour JL and Slovis CM. Arterial Blood Gas Analysis. J Respir Dis ;2: epub.

6. Limitations of Traditional Pulse Oximetry
Calibration assumptions
Measurements in young volunteers
Use of empirical calibration curves
Optical interference
Dyshemoglobinemias
Bilirubin and intravenous dyes
Signal artifact
False signal
Low signal to noise ratio
Young volunteers include olympic athletes
Researchers could only get volunteers down to SaO2 of 75-80% - though likely we care little clinically below this point anyway
Hyperbilirubinemia does not appear to interfere with pulse oximetry except that produce CO and can artifactually increase MetHb
Intravenous dyes:
Methylene blue has high absorbance at 660nm and causes impressive spurious decrease in SpO2
Indocyanine green and indigo carmine also cause spurious decreased SpO2
False signal:
lights of any kind including surgical lamps, fiberoptic instruments and sunlight
optical shunt: inappropriately placed so not through tissue at all
nonartial pulsation:
Motion artifact:
if does occur then ratio moves toward 1 which drives SpO2 to 85%
tonic clonic seizure does not affect (? Shivering)
CPR does affect
helicopter flight does not appear to affect
arterial pulsations transmitted to venous (venous congestion)
tricuspid regurgitation

7. Limitations of Traditional Pulse Oximetry
Dyshemoglobinemias
Functional
Oxyhemoglobin
Deoxyhemoglobin
Non-functional
Carboxyhemoglobin
Methemoglobin

8. Limitations of Traditional Pulse Oximetry
Carboxyhemoglobin
Image source:

9. Limitations of Traditional Pulse Oximetry
Carboxyhemoglobin

10. Limitations of Traditional Pulse Oximetry
Carboxyhemoglobin
endogenous source is breakdown of heme
Typical levels 1-2% in nonsmokers
Dennery 2001

11. Limitations of Traditional Pulse Oximetry
Carboxyhemoglobin
endogenous source is breakdown of heme
Typical levels 1-2% in nonsmokers

12. Limitations of Traditional Pulse Oximetry
Carboxyhemoglobin
Typically associated with exposure to exogenous carbon monoxide
Levels in most non-smokers: 1-2%
Levels in heavy smokers: up to 10-20%
Increased in cirrhosis by 2%
Image sources: townipproject.wikispaces.com, tobaccofreewny.com, woodstove.net

13. Limitations of Traditional Pulse Oximetry
Image source:

14. Limitations of Traditional Pulse Oximetry

15. Limitations of Traditional Pulse Oximetry
Carboxyhemoglobin
Absorbs light at 660nm much like oxyhemoglobin
Effect on measured oxygen saturation (SpO2) is to overestimate true oxygen saturation
Overestimation is approximately proportional to the carboxyhemoglobin level (COHb)
SpO2 = SaO2 + %COHb
In rats: oximeter read SpO2 90% in the presence of a COHb of 70% and O2Hb level of only 30%

16. Limitations of Traditional Pulse Oximetry
Carboxyhemoglobin
causes relative hypoxia due to carbon monoxide’s affinity for hemoglobin
triggers inflammation through multiple pathways resulting in cardiac and neurologic injury

17. Limitations of Traditional Pulse Oximetry
Methemoglobin
Image source:

18. Limitations of Traditional Pulse Oximetry
Methemoglobin
Methemoglobin formed when iron is hemoglobin is oxidized from ferrous to ferric state

19. Limitations of Traditional Pulse Oximetry
Methemoglobin
Congenital
Exposure to a number of different agents
Antibiotics – especially sulfa
Local anesthetics
Nitrates
congenital causes such as deficiency of cytochrome b5 reductase or a mutation in one of the globin molecules, known as hemoglobin M disease
dapsone and the topical anesthetics benzocaine and lidocaine
Other classical drug causes of methemoglobinemia include antibiotics (trimethoprim, sulfonamides and dapsone[2]), local anesthetics (especially articaineand prilocaine[3]), and others such as aniline dyes, metoclopramide, chlorates and bromates. Ingestion of compounds containing nitrates (such as the patina chemical bismuth nitrate) can also cause methemoglobinemia.

20. Limitations of Traditional Pulse Oximetry

21. Limitations of Traditional Pulse Oximetry
At 660nm MetHb absorbs light similarly to reduced hemoglobin

22. Limitations of Traditional Pulse Oximetry
But at 940nm the absorbance/extinction of MetHb is markedly greater than either oxyhemoglobin or reduced hemoglobin.

23. Limitations of Traditional Pulse Oximetry
Methemoglobin
Increases both numerator and denominator of the ratio of relative absorbances
Drives ratio toward 1 which results in measured SpO2 of 85%

24. Pulse CO-Oximetry Masimo Rainbow® SET Pulse CO-Oximetry
Introduced in 2005
Rainbow: uses 8 wavelengths of light
SET: Signal Extraction Technology

25. Pulse CO-Oximetry
Masimo Radical 7

26. Pulse CO-Oximetry
Image source:

27. Pulse CO-Oximetry Measurements Total hemoglobin (SpHb)
Oxygen content (SpOC)
Oxygen saturation (SpO2)
Carboxyhemoglobin (SpCO)
Methemoglobin (SpMet)
Photoplethysmographic (Pleth) variability index (PVI)
Perfusion index (PI)
Pulse rate (PR)

28. Pulse CO-Oximetry Measurements Total hemoglobin (SpHb)
Oxygen content (SpOC)
Oxygen saturation (SpO2)
Carboxyhemoglobin (SpCO)
Methemoglobin (SpMet)
Photoplethysmographic (Pleth) variability index (PVI)
Perfusion index (PI)
Pulse rate (PR)

29. Pulse CO-Oximetry Measurements Total hemoglobin (SpHb)
Oxygen content (SpOC)
Oxygen saturation (SpO2)
Carboxyhemoglobin (SpCO)
Methemoglobin (SpMet)
Photoplethysmographic (Pleth) variability index (PVI)
Perfusion index (PI)
Pulse rate (PR)

30. Applications of Pulse CO-Oximetry
Total hemoglobin – need
Among the most commonly checked laboratory values
Current methods invasive, time consuming and intermittent
Blood draws result in significant hospital acquired anemia

31. Conclusion: Blood loss from greater use of phlebotomy is independently associated with the development of HAA. These findings suggest that HAA may be preventable by implementing strategies to limit blood loss from laboratory testing.

32. Applications of Pulse CO-Oximetry
Total hemoglobin – evidence for
Macket 2007: first clinical validation study
Macket 2010: pulse co-oximetry based SpHb is accurate within 1.0 g/dL in health volunteers undergoing hemodilution
Causey 2011: appears accurate in general surgery population
Frasca 2011: pulse co-oximetry based SpHb in ICU patients without ongoing bleeding
Macket 2007 (loma linda, california): 30 med-surg patient, 18 healthy volunteers with hemodilution
Macket 2010: 20 healthy volunteers, 165 measurements. ~500cc of blood withdrawn from each subject. Given up to 30cc/kg IV fluid back. Compared to lab co-oximeter
Causey 2011 (Madigan): surgical and ICU patients. Data were collected on 60 patients (OR = 25 and ICU = 45). The overall correlation of the Masimo SpHb and the laboratory Hb was .77 (P < .001) in the OR group with a mean difference of .29 g/dL (95% confidence interval [CI], ). The overall correlation in the ICU group was .67 (P < .001) with a mean difference of .05 g/dL (95% CI, -.22 to -.31).
Frasca 2011 (france): 62 patients in med-surg ICU, 471 blood samples, non-invasive better than other point of care device and compared to satellite lab but similar to laboratory (bias 0.0 and limits of agreement +/- 1.0 for pulse co-oximeter compared to lab)

33. Applications of Pulse CO-Oximetry
Total hemoglobin – evidence against
Lamhaut 2011:
Small systematic bias
Significant lack of precision
Significant number of outliers
Gayat 2011:
Moderate systematic bias
Difficulty obtaining in “sicker” patients
Lamhaut 2011 (france): Eighty-five simultaneous measurements from SpHb, HemoCue®, and the laboratory were obtained from 44 patients. Bland and Altman comparison of SpHb and HemoCue® with the laboratory measurement showed, respectively, bias of ± 1.39 g · dl and ± 1.05 g · dl, and a precision of 1.11 ± 0.83 g · dl and 0.67 ± 0.83 g · dl. Considering an acceptable difference of ± 1.0 g · dl with the laboratory measurement, the percentage of outliers was significantly higher for SpHb than for HemoCue® (46% vs. 16%, P < 0.05).
Gayat 2011 (france): (1) no value was obtained for 8% of the patients; these patients were older and had a lower SpO2, a lower arterial pressure, and a lower hemoglobin concentration than those for whom a measurement could be obtained; (2) hemoglobin measurements with the Masimo Radical-7 Pulse CO-Oximeter are systemically biased, and moreover, the coefficient of variation of this method is not in accordance with the required standard, fixed at 1.4%. The mean average bias and lower and upper limits of agreement were, respectively, 18.0 g/L (15.1 to 20.9 g/L), −32.9 g/L (−37.9 to −27.9 g/L), and 68.9 g/L (63.9 to 73.9 g/L). The intraclass correlation coefficient was 0.53 (0.10 to 0.74).

34. Applications of Pulse CO-Oximetry
Total hemoglobin – evidence for further research
Miller 2011:
Not accurate enough for all clinical scenarios
Accuracy appears to improve with time
Data consisted of 78 measurements of SpHb, tHb, and HCue made on the 20 patients. Absolute differences between SpHb and tHb were <1.5 g/dL for 61% of observations, between 1.6 to 2.0 g/dL for 16% and >2.0 g/dL for 22% of the observations. Observed differences displayed significant decreases with time and higher perfusion index values. No systematic relationships were observed with age or weight. Except for 1 value, all of the HCue values were <1.0 g/dL of tHb.

35. Applications of Pulse CO-Oximetry
Total hemoglobin – ongoing work
Non-invasive measurement of total hemoglobin in the ICU setting
Blinded
Prospective
ICU patients receiving blood transfusion
Ongoing subject enrollment
Preliminary results suggest significant lack of precision in noninvasive measurements due to outliers*
*Preliminary data

36. Applications of Pulse CO-Oximetry

37. Applications of Pulse CO-Oximetry

38. Applications of Pulse CO-Oximetry
Carboxyhemoglobin – toxicity
causes relative hypoxia due to carbon dioxide’s affinity for hemoglobin
triggers inflammation through multiple pathways resulting in cardiac and neurologic injury
Symptoms are nonspecific:
mild headache, nausea, confusion, dizziness
MI, stroke, death

39. Applications of Pulse CO-Oximetry
Carboxyhemoglobin – evidence for
Case reports of noninvasive measurement resulting in diagnosis
Crawford 2008: CO poisoning onboard submarine
Roth 2009: CO poisoning due to water heater
Roth 2011: acceptable bias and precision for screening for CO poisoning in ED
Suner 2007: acceptable correlation for screening for CO poisoning in ED
Roth (austria): 1578 subjects. 17 diagnosed with CO poisoning
Suner (brown): patients, R 0.77

40. Applications of Pulse CO-Oximetry
Carboxyhemoglobin – evidence against
Touger 2010: sensitivity of only 43% for patients with lab values of COHb greater than 15%
NB: enrollment was for suspected CO poisoning
Touger (Jacobi Medical Center): 120 patients with suspected carbon monoxide poisoning. 10% had difficulty acquiring signal. Limits of agreement were -11.6% to 14.4%. Only correctly identified 11 of 23 patients with COHb values greater than 15%

41. Applications of Pulse CO-Oximetry
Carboxyhemoglobin – transfusion
Reports of alarming levels of carboxyhemoglobin in banked blood
Large volume transfusion may lead to prolonged increases in COHb levels
Average level 0.78% but 10% had level greater than 1.5% and the highest recorded was 12%
Carboxyhemoglobinlevels decrease with storage but methemoglobin levels increase
Large transfusion effect both from elevated levels in banked blood and from breakdown of heme
Most clinically significant in pediatric cardiac surgery population but still of interest

42. Applications of Pulse CO-Oximetry
Carboxyhemoglobin – ongoing research
Non-invasive measurement of carboxyhemoglobin in the ICU setting
Blinded
Prospective
ICU patients receiving blood transfusion
Ongoing subject enrollment
Inadequate data for preliminary results

43. Applications of Pulse CO-Oximetry
Carboxyhemoglobin – DLCO
ATS/ERS Task Force on Standardization of Lung Function Testing recommended adjusting DLCO for total hemoglobin and COHb
COHb in particular increases “back pressure”
Mahoney 2007: noninvasive COHb measurements may affect categorization of DLCO impairment
Retrospective
No laboratory correlation

44. Applications of Pulse CO-Oximetry
Carboxyhemoglobin – DLCO
Effect of noninvasively assessed carboxyhemoglobin levels on diffusing capacity measured during pulmonary function testing
Prospective
Spot observation at time of PFT
Both SpHb and COHb
Frequent laboratory correlation
Ongoing subject enrollment
Preliminary results suggest that lack of precision in noninvasive measurements limits utility of device

45. Conclusions
Pulse co-oximetry represents a significant advancement in oximetry technology
Noninvasive measurement of total hemoglobin in particular requires further investigation and validation prior to widespread use
Pulse co-oximetry may provide useful screening information in low risk populations
Note systematic bias was to read low

46. Future Areas of Research
Sensor technology
Rev E resposable sensor
Rev G resposable sensor

47. Future Areas of Research
Total hemoglobin
Guidance of blood transfusion in patients with GI bleed
Screening for anemia prior to blood donation
Pleth variability index
Comparison to pulse variability index monitors

48. Acknowledgements VA Puget Sound Health Care System Erik Swenson, M.D.
Richard Goodman, M.D.
Robin Boland
Christopher Click
Diane Houk
Barb
Shelly

49. Acknowledgements UW Internal Medicine Residency Masimo Family
D. Scott Weigle, M.D.
Christopher Knight, M.D.
Tyler Albert, M.D.
Masimo
Jolene Hagin, R.N.
Serop Gharibian
Family
Katie Ash Greenzang, M.D.
Sarah Ash, Ph.D.

50. References
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Causey MW et al. Validation of noninvasive hemoglobin measurements using the Masimo Radical-7 SpHb Station. Am J Surg 2011; 201:592-8.
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Lamhaut L et al. Comparison of the Accuracy of Noninvasive Hemoglobin Monitoring by Spectrophotometry (SpHb) and HemoCue® with Automated Laboratory Hemoglobin Measurement. Anesthesiology 2011; 115:

51. References
Macket MR, Allard M, Applegate RL and Rook J. The Accuracy of Noninvasive and Continuous Total Hemoglobin Measurement by Pulse CO-Oximetry in Human Subjects Undergoing Hemodilution. Anesth Analg 2010; 111:
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Scheller MS, Unger RJ, Kelner MJ. Effects of Intravenously Administered Dyes on Pulse Oximetry Readings. Anesthesiology 1986;65:

52. References
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