title: Factors affecting the performance of 5 cerebral oximeters during hypoxia in healthy volunteers.
abstract: BACKGROUND
  Cerebral oximetry is a noninvasive optical technology that measures frontal cortex blood hemoglobin-oxygen saturation. Commercially available cerebral oximeters have not been evaluated independently. Unlike pulse oximeters, there are currently no Food and Drug Administration standards for performance or accuracy. We tested the hypothesis that cerebral oximeters accurately measure a fixed ratio of the oxygen saturation in cerebral mixed venous and arterial blood.
  
  
  METHODS
  We evaluated the performance of 5 commercially available cerebral oximeters: the EQUANOX® 7600 in 3- and 4-wavelength versions (Nonin Medical, Plymouth, MN), FORE-SIGHT® (Casmed, Branford, CT), INVOS® 5100C (Covidien, Boulder, CO), and the NIRO-200NX® (Hamamatsu Photonics, Hamamatsu City, Japan) during stable isocapnic hypoxia in volunteers. Twenty-three healthy adults (14 men, 9 women) had sensors placed on each side of the forehead. The subject's inspired oxygen (FIO2) was then changed to produce 6 steady-state arterial oxygen saturation (SaO2) levels between 100% and 70%, while end-tidal CO2 was maintained constant. At each plateau, simultaneous blood samples from the jugular bulb and radial artery were analyzed with a hemoximeter (OSM-3, Radiometer Medical A/S, Copenhagen, Denmark). Each cerebral oximeter's bias was calculated as the difference between the instrument's reading (cerebral saturation, ScO2) with the weighted saturation of venous and arterial blood (Sa/vO2), as specified by each manufacturer (INVOS: 25% arterial/75% venous; FORE-SIGHT, EQUANOX, and NIRO: 30% arterial/70% venous).
  
  
  RESULTS
  Five hundred forty-two comparisons between paired blood samples and oximeter readings were analyzed. The pooled root mean square error was 8.06%, a value higher than for pulse oximeters, which is ±3% by Food and Drug Administration standards. The mean % bias ± SD (precision) and root mean square errors were: FORE-SIGHT 1.76 ± 3.92 and 4.28; INVOS 0.05 ± 9.72 and 9.69; NIRO-200NX -1.13 ± 9.64 and 9.68; EQUANOX-3 λ 2.48 ± 8.12 and 8.47; EQUANOX-4 λ 2.84 ± 6.27 and 6.86. The FORE-SIGHT, NIRO-200NX, and EQUANOX-3 λ had significantly more positive bias at lower SaO2. The amount of bias during hypoxia was reduced when the bias was calculated on the basis of difference between oximeter reading and the arterial and mixed venous saturation difference rather than the weighted average of blood saturation, indicating that differences in the ratio between arterial and venous blood volumes account for some of the positive bias at low saturation. Dark skin pigment tended to produce more negative bias in all instruments but bias was significantly larger than zero only for the FORE-SIGHT oximeter. Bias was significantly more negative in women for INVOS and EQUANOX devices but not for the FORE-SIGHT device.
  
  
  CONCLUSIONS
  While responsive to desaturation, cerebral oximeters exhibited large variation in reading errors between subjects, with mean bias possibly related to variations in the ratio of arterial and venous blood in the sampling area of the brain. This ratio is probably not fixed, as assumed by the manufacturers, but dynamically changes with hypoxia. Better understanding these factors could improve the performance of cerebral oximeters and help establish saturation or blood flow thresholds for brain well-being.
authors.affiliation: From the Department of Anesthesia and Perioperative Care, Severinghaus-Radiometer Research Laboratories and the UCSF Hypoxia Research Laboratory, University of California at San Francisco, San Francisco, California.
authors.forename: Philip E
authors.initials: PE
authors.lastname: Bickler
authors.forename: John R
authors.initials: JR
authors.lastname: Feiner
authors.forename: Mark D
authors.initials: MD
authors.lastname: Rollins
mesh_terms: D000328:Adult; D001921:Brain / Q000378:metabolism; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000097:blood* / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D010092:Oximetry / Q000295:instrumentation* / Q000379:methods* / Q000592:standards; D010101:Oxygen Consumption; D012737:Sex Factors; D012880:Skin Pigmentation / Q000502:physiology; D055815:Young Adult
references.citation: Chance B. Spectrophotometry of intracellular respiratory pigments. Science. 1954;120:767–75
references.citation: Jöbsis FF. Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters. Science. 1977;198:1264–7
references.citation: Boas DA, Franceschini MA. Haemoglobin oxygen saturation as a biomarker: the problem and a solution. Philos Trans A Math Phys Eng Sci. 2011;369:4407–24
references.citation: Devor A, Sakadžić S, Srinivasan VJ, Yaseen MA, Nizar K, Saisan PA, Tian P, Dale AM, Vinogradov SA, Franceschini MA, Boas DA. Frontiers in optical imaging of cerebral blood flow and metabolism. J Cereb Blood Flow Metab. 2012;32:1259–76
references.citation: Yao FS, Tseng CC, Ho CY, Levin SK, Illner P. Cerebral oxygen desaturation is associated with early postoperative neuropsychological dysfunction in patients undergoing cardiac surgery. J Cardiothorac Vasc Anesth. 2004;18:552–8
references.citation: Goldman S, Sutter F, Ferdinand F, Trace C. Optimizing intraoperative cerebral oxygen delivery using noninvasive cerebral oximetry decreases the incidence of stroke for cardiac surgical patients. Heart Surg Forum. 2004;7:E376–81
references.citation: Fischer GW, Lin HM, Krol M, Galati MF, Di Luozzo G, Griepp RB, Reich DL. Noninvasive cerebral oxygenation may predict outcome in patients undergoing aortic arch surgery. J Thorac Cardiovasc Surg. 2011;141:815–21
references.citation: Murkin JM, Adams SJ, Novick RJ, Quantz M, Bainbridge D, Iglesias I, Cleland A, Schaefer B, Irwin B, Fox S. Monitoring brain oxygen saturation during coronary bypass surgery: a randomized, prospective study. Anesth Analg. 2007;104:51–8
references.citation: Heringlake M, Garbers C, Käbler JH, Anderson I, Heinze H, Schön J, Berger KU, Dibbelt L, Sievers HH, Hanke T. Preoperative cerebral oxygen saturation and clinical outcomes in cardiac surgery. Anesthesiology. 2011;114:58–69
references.citation: Pennekamp CW, Bots ML, Kappelle LJ, Moll FL, de Borst GJ. The value of near-infrared spectroscopy measured cerebral oximetry during carotid endarterectomy in perioperative stroke prevention. A review. Eur J Vasc Endovasc Surg. 2009;38:539–45
references.citation: Lewis SB, Myburgh JA, Thornton EL, Reilly PL. Cerebral oxygenation monitoring by near-infrared spectroscopy is not clinically useful in patients with severe closed-head injury: a comparison with jugular venous bulb oximetry. Crit Care Med. 1996;24:1334–8
references.citation: Mittnacht AJ. Near infrared spectroscopy in children at high risk of low perfusion. Curr Opin Anaesthesiol. 2010;23:342–7
references.citation: Davie SN, Grocott HP. Impact of extracranial contamination on regional cerebral oxygen saturation: a comparison of three cerebral oximetry technologies. Anesthesiology. 2012;116:834–40
references.citation: Sørensen H, Secher NH, Siebenmann C, Nielsen HB, Kohl-Bareis M, Lundby C, Rasmussen P. Cutaneous vasoconstriction affects near-infrared spectroscopy determined cerebral oxygen saturation during administration of norepinephrine. Anesthesiology. 2012;117:263–70
references.citation: Kim MB, Ward DS, Cartwright CR, Kolano J, Chlebowski S, Henson LC. Estimation of jugular venous O2 saturation from cerebral oximetry or arterial O2 saturation during isocapnic hypoxia. J Clin Monit Comput. 2000;16:191–9
references.citation: Feiner JR, Severinghaus JW, Bickler PE. Dark skin decreases the accuracy of pulse oximeters at low oxygen saturation: the effects of oximeter probe type and gender. Anesth Analg. 2007;105:S18–23
references.citation: Matta BF, Lam AM. The rate of blood withdrawal affects the accuracy of jugular venous bulb. Oxygen saturation measurements. Anesthesiology. 1997;86:806–8
references.citation: Bland JM, Altman DG. Agreement between methods of measurement with multiple observations per individual. J Biopharm Stat. 2007;17:571–82
references.citation: Bickler PE, Feiner JR, Severinghaus JW. Effects of skin pigmentation on pulse oximeter accuracy at low saturation. Anesthesiology. 2005;102:715–9
references.citation: Henson LC, Calalang C, Temp JA, Ward DS. Accuracy of a cerebral oximeter in healthy volunteers under conditions of isocapnic hypoxia. Anesthesiology. 1998;88:58–65
references.citation: Ito H, Ibaraki M, Kanno I, Fukuda H, Miura S. Changes in the arterial fraction of human cerebral blood volume during hypercapnia and hypocapnia measured by positron emission tomography. J Cereb Blood Flow Metab. 2005;25:852–7
references.citation: Ito H, Kanno I, Fukuda H. Human cerebral circulation: positron emission tomography studies. Ann Nucl Med. 2005;19:65–74
references.citation: Willie CK, Macleod DB, Shaw AD, Smith KJ, Tzeng YC, Eves ND, Ikeda K, Graham J, Lewis NC, Day TA, Ainslie PN. Regional brain blood flow in man during acute changes in arterial blood gases. J Physiol. 2012;590:3261–75
references.citation: Butwick A, Hilton G, Carvalho B. Non-invasive haemoglobin measurement in patients undergoing elective Caesarean section. Br J Anaesth. 2012;108:271–7