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

Disclosures No financial disclosures. Research presented is unfunded.

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

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

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 2008. 29;2: epub.

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

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

Limitations of Traditional Pulse Oximetry Carboxyhemoglobin Image source: http://www.wissensdrang.com/wisbr1.htm

Limitations of Traditional Pulse Oximetry Carboxyhemoglobin

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

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

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

Limitations of Traditional Pulse Oximetry Image source: http://web.squ.edu.om/med-Lib/MED_CD/E_CDs/anesthesia/site/content/v03/030220r00.HTM

Limitations of Traditional Pulse Oximetry

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%

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

Limitations of Traditional Pulse Oximetry Methemoglobin Image source: http://alexandria.healthlibrary.ca/documents/notes/bom/unit_2/L-03%20HEMOGLOBIN1.xml

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

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.

Limitations of Traditional Pulse Oximetry

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

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

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%

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

Pulse CO-Oximetry Masimo Radical 7

Pulse CO-Oximetry Image source: http://www.masimo.co.uk/Rainbow/about.htm

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)

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)

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)

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

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.

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], .08-.49). 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)

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 -0.02 ± 1.39 g · dl and -0.17 ± 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).

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.

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

Applications of Pulse CO-Oximetry

Applications of Pulse CO-Oximetry

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

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): 10856 patients, R 0.77

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%

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

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

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

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

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

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

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

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

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.

References Barker and Badal. The Measurement of Dyshemoglobins and Total Hemoglobin by Pulse Oximetry. Curr Opin Anaesthesiol 21:805-810. Barker SJ, Tremper KK, Hyatt J: Effects of Methemoglobinemia on Pulse Oximetry and Mixed Venous Oximetry. Anesthesiology 1989;70:112-117. Causey MW et al. Validation of noninvasive hemoglobin measurements using the Masimo Radical-7 SpHb Station. Am J Surg 2011; 201:592-8. Crawford DM and Hampson NB. Fire and Ice: Diagnosis of Carbon Monoxide Poisoning in a Remote Environment. Emerg Med J 2008; 25:235-236. Dennery PA, Seidman DS and Stevenson DK. Neonatal Hyperbilirubinemia. N Engl J Med 2001; 344:581-590. Ehlers M, Labaze G, Hanakova M, McCloskey D and Wilner G. Alarming Levels of Carboxyhemoglobin in Banked Blood. J Cardiothorac Vasc Anesth 2009; 23:336-338. Ernst A and Zibrak JD. Carbon Monoxide Poisoning. N Eng J Med 1998; 339:1603-1608. Frasca D et al. Accurace of a Continuous Noninvasive Hemoglobin Monitor in Intensive Care Unit Patients. Crit Care Med 2011; 39(10):1-6. Gayat E et al. Performance Evaluation of a Noninvasive Hemoglobin Monitoring Device. Ann Emerg Med 2011; 57:330-333. Lamhaut L et al. Comparison of the Accuracy of Noninvasive Hemoglobin Monitoring by Spectrophotometry (SpHb) and HemoCue® with Automated Laboratory Hemoglobin Measurement. Anesthesiology 2011; 115:548-54.

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; 111:1424-1167. Mahoney AM, Stimpson CL, Scott KL and Hampson NB. Noninvasive Measurement of Carboxyhemoglobin Levels for Adjustment of Diffusion Capacity Measured During Pulmonary Function Testing. Resp Care 2007; 52:1741-1743. Miller et al. A Comparison of Three Methods of Hemoglobin Monitoring in Patients Undergoing Spine Surgery. Anesth Analg 2011; 112:858–863. Ortega R, Hansen CJ, Elterman K and Woo W. Videos in Clinical Medicine: Pulse Oximetry. N Eng J Med 2011;364:e33. Roth et al. Accuracy of Noninvasive Multiwave Pulse Oximetry Compared With Carboxyhemoglobin from Blood Gas Analysis in Unselected Emergency Department Patients. Ann Emerg Med 2011; 58:74-79. Roth et al. Victim of Carbon Monoxide Poisoning Identified by Carbon Monoxide Oximetry. J Emerg Med 2009; 40:640-642. Salisbury AC et al. Diagnostic Blood Loss From Phlebotomy and Hospital-Acquired Anemia During Acute Myocardial Infarction. Arch Int Med 2011; Epub ahead of print. Scheller MS, Unger RJ, Kelner MJ. Effects of Intravenously Administered Dyes on Pulse Oximetry Readings. Anesthesiology 1986;65:550-552.

References Severinghaus JW. Takuo Aoyagi: Discovery of Pulse Oximetry. Anesth and Analg 2007;105:S1-4. Sinex JE. Pulse Oximetry: Principles and Limitation;17:59-65. Suner et al. Non-Invasive Pulse CO-Oximetry Screening in the Emergency Department Identifies Occult Carbon Monoxide Toxicity. J Emerg Med 2007; 34:441-450. Touger et al. Performance of the RAD-57 Pulse CO-Oximeter Compared with Standard Laboratory Carboxyhemoglobin Measurement. Ann Emerg Med 2010; 20(10):1-7. Tram TT et al. Carboxyhemoglobin and Its Correlation to Disease Severity in Cirrhotics. J Clin Gastroenterol 2007; 41:211-215. Ziemann-Gimmel P and Schwartz DE. Increased Carboxyhemoglobin in a Patient with a Large Retroperitoneal Hematoma. Anesth Analg 2004;99:1800-1802.

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