January 1989
`
`ANESAV
`
`ISSN 0003-3022
`
`The American Society of
`
`Anesthesiologists,
`
`Inc.
`
`Volume ’70
`
`Number 1
`
`US. Patent No. 8,989,830
`
`Apple Inc.
`APL1017
`U.S. Patent No. 8,989,830
`
`Pages3.
`
`:
`
`’
`
`0001
`
`APL1017
`
`FITBIT, Ex. 1017
`
`

`

`Anenliesioliiy
`
`THE JOURNAL OF
`THE AMERICAN SOCIETY or ANESTHESIOLOGISTS, INC.
`Editor-in-Chief
`
`LAWRENCE]. SAIDMAN, M.D., San Diego. California
`Editors
`
`David E. Longnecker, MD.
`julien F. Biebuyck, M.B.. D.Phil.
`Philadelphia, Pennsylvania
`Hershey, Pennsylvania
`Dennis T. Mangano, Ph.D., MD.
`johnj. Downes. M.D.
`San Francisco, California
`Philadelphia. Pennsylvania
`Kai Rehder, M.D.
`H. Barrie Fairley, M.B.. B.S.
`Rochester, Minnesota
`Stanford, California
`Donald R. Stanslti, MD.
`Simon Gelman, M.D.. Ph.D.
`Stanford, California
`Birmingham, Alabama
`Michael M. Todd, MD.
`Carol A. Hirshman. MD.
`Iowa City. Iowa
`Baltimore. Maryland
`Warren M. Zapol, M.D., Boston, Massachusetts
`
`Associate Editors
`
`Charles W. Buffington, MD.
`Pittsburgh, Pennsylvania
`David H. Chestnut, M.D.
`Iowa City, Iowa
`Jamey BI Cooper) phi),
`Boston, Massachusetts
`Dennis M. Fisher. M.D.
`San Francisco, California
`Tony L. Yaksh, Ph.D.
`Thomas F. Hornbein, MD.
`
`San Diego. California
`Seattle, Washington
`
`Carl Lynch III, MD. Ph.D.
`Charlottesville, Virginia
`Mervyn Maze, M.B., Ch.B.
`Stanford, California
`Henry Rosenberg, MD.
`Philadelphia, Pennsylvania
`Gary R. Strichartz, Ph.D.
`Boston, Massachusetts
`
`
`correspondence relating to editorial management. and Letters to the Editor should be mailed to Lawrence
`Manuscripts for publication.
`12015, University of Ca!ifornia—-San Diego, San Diego, Caiifornia 92093. Books for review should
`J. Saidman, M.D.. Anesthesiology.
`_
`The Children's Hospital of Phiiadelphia. One Children's Flam. 34th
`be mailed to john j. Downes. M.D.. Department of Anesthesia.
`I
`‘
`I
`Street and Civic Center Boulev
`.
`_
`_
`Pa" 19104.
`_
`All articles are accepted for publication with the understanding that they are contributed exclusively to this journal and become the.
`1m“ swtemenls 0“ Opinion-5' expressed an the Journal reflect the views of the
`'
`So e: of Anesthesiologists.
`'
`'
`American
`Propertyr of the American
`ci y
`Slade“! of Anathesmlogim unless so Emmi
`aulhor s and d not re resent officlal P01“? 0f the
`.
`.
`,
`_
`For (damn, 3.3.1 recorEmendations cementing the preparation of manuscripts see GUIDE FOR AUTHORS. which appears “1 the january
`and
`’
`.
`.
`.
`.
`Aétlgtrsfiplesgnd related correspondence should be addressed to Advertismg Manager. ANESTHESIOLOGV. j. B. Lippincott Company.
`E33l washin Eon 5 am: Philadelphia, Pa. 19105. Publication ofan advertisement in Anesrflrsmcoov does not constitute endorsement
`by ANESTHESIOLOEY of the Product described therein or of any representations made by the advertiser with respect to the product.
`_______________—
`ISSN 00034022) is published 13 times a year (monthly except September. in which two issues are published)
`ANESTHESIOLOGY (
`incott Company. at Downsville Pike. Route 3. Box 20-3. Hagerstown.
`calhflioloym'lnc'J‘JH'E'sltiipp
`Ph'l d l 11'
`PA 19105 9' ed'
`h U s A or;
`' h
`POT the American Society of A“
`located at East Washington
`uare.
`1a ep :3.
`. mm in t e
`.
`_
`‘opyng ; 1939
`MD
`‘
`by “:1lgégcfirgzififgjscsmesiologim. Inc, Second class postage paid at Hagerstown. MD. and at additional mailing offices.
`'
`han e of address shouid be mailed to the Execut'
`_
`N t
`, All correspondence related to membership'and c ‘
`we
`I
`SC:1-1:;ref Egg-E;:2(132:;ngAnesthesiologism 515 Bussc Highway, Park Ridge. Illinois 50068. Correspondence regarding nonmember
`rml Fulfillment Department. LippincotL/Harper. Downsville Pike. Rome 3. Box 20-3. Hagen-grown,
`.
`.
`fig;f;fi30;i§;23u;fi :llStiT-igég-Jfiggdoao; in Maryland, call collect 301-824-7300. Correspondence regarding noninember subscriptions
`.
`_
`_
`,
`.
`.
`t subs“; [ion rates and subscription orders, should be sent to Woodbell' Incorporated, 4-22.] 1. Kimkasai,
`Eligxéll‘lclflzgénfi;iflj::::uln IndiaFNePaL Bangladesh, and Sri Lanlta contact Universal Subscription Agency Pvt. Ltd.. 101-102
`C
`'
`,N w Delhi—110017. india.
`.
`‘
`I
`Agility:Ethirfdhigjiliabfis $10.00 individual. $50.00 institution: all other countries exceptjapan. India. Nepal, Bangladesh, and
`.
`.
`-
`A
`‘l delive
`_
`‘
`'
`available it
`it re
`est.
`-
`'
`'
`5.00 institution. Single copies $8.00. Rates for alr man
`ry _
`_
`_
`po
`qu
`_
`13f]:It1":“Soclmief,7Estii‘iclengi'viggall’hfilsisher receives a refill“?st for “Placement "mun 60921” or the mum; in the U‘ 5' or “thin 90 days in
`a“ othcr couturies and the original issue is returned by the postal service as undeliverable, the issue will be replaced.
`-
`'
`'
`-B Ha erstown MD 21740.
`P
`.
`hart es to Anesthesiology. Downmne Pike' Rome 3' Box 20
`'
`g
`-
`'
`-
`i
`ii). milozcucigicifefns fgr internal or Personal use. 01" 1hr Imemal 0" Personal use Of speafic dwms'
`'5 granted by The
`American Society ofAnesthesiologists for librariesand other users registered with the Copyright Clearance Center (CCC) Transactional
`,
`.
`.
`r
`f $0030 Per copy, plus $00.05 per page is paid directly to CCC. 21 Congress Si... Salem,
`amrigi¥05313r5§hgagifiggdsgtagghibgg‘g;(ll-his does not extend to other kinds of copying. such as copying for general distribution.
`for advertising or Promotional purposes, for creating new collective works. or for resale.
`0002
`0002
`
`
`
`FITBIT, EX. 1017
`
`FITBIT, Ex. 1017
`
`

`

`Juvstfiesiolow
`
`
`
`3
`
`January 1989
`
`EDITORIAL VIEWS
`
`CONTENTS
`
`A Change in Format for ANESTHESIOLOGY.
`Lawrence]. Saidrnan
`
`Changing Perspectives in Monitoring Oxygenation.
`H. Barrie Fairley
`
`Studies in Animals Should Precede Human Use of Spinally Administered Drugs.
`Tony1 L. Yaksh and]. G. Collins
`
`CLINICAL INVESTIGATIONS
`
`The Influenc
`
`Pipecuro
`Oxide.
`
`e of Renal Failure on the Pharmacokinetics and Duration of Action of
`nium Bromide in Patients Anesthetized with Halothane and Nitrous
`
`I
`
`ell, P. Clover Canfell, Kay P. Caslagnoli, Daniel P. Lynam, Mark R
`and Ronald D. Miller
`fame: E. Golda!
`Fahey, Dennis M. Fisher,
`Effect of Intercostal NCTVE Blockade on Respiratory Mechanics and CO2 Chemosen»
`sitivity at Rest and Exercise.
`Bernice R. Heeker, Robert Bjurstrorn, and Robert B. Seltoene
`Electrocardiographic, Mechanical, and Metabolic In-
`Comparison of Hemodynamic,Myocardial lschemia in Vascular Surgical Patients with
`dicators of Intraoperative
`Coronary Artery Disease.
`r, Margareta Oatmeal, Arnold Friedman, George Diamond,
`Sti‘ren Haggmark, Per Hohne
`Edward Lowenslein, and Sebastian Rel:
`mall Doses of Sufentanil or Fentanyl: Dose Versus EEG
`and Thiopental Requirement.
`
`Induction of Anesthesia with S
`Response, Speed of Onset,
`T. Andrew Bowdle and Richard]. Ward
`elationship of Mivacurium Chloride in Humans during Nitrous
`The Dose-Response R
`Nitrous Oxide—Enflurane Anesthesia.
`OxideeFentanyI or
`B. Kills, Torn Heler, Mark R. Fahey, Daniel P. Lynam, and
`james E. Caldwell, john
`Ronald D. Miller
`
`Transurethral Resection of th
`Potentials.
`janice Mei-Li Wang, Donnell ]. Creel, and K. C. Wong
`
`e Prostate, Serum Glycine Levels, and Ocular Evoked
`
`l3
`
`19
`
`26
`
`3 l
`
`36
`
`——/——-
`
`0003
`0003
`
`FITBIT. EX. 1017
`
`(Continued on page 5)
`
`FITBIT, Ex. 1017
`
`

`

`January 1989—ANESTHESIOLOGY
`
`CONTENTS
`
`0‘
`
`(Continued from page 3)
`
`Lower Esophageal Contractility Predicts Movement during Skin Incision in Patients
`Anesthetized with Halothane, but Not with Nitrous Oxide and Alfentanil.
`Daniel I. Sessler, Randi Swen, Christine 1’. Olifsson, and Franklin Chow
`
`Determination of Inna-abdominal Pressure Using a Transurethral Bladder Catheter:
`Clinical Validation of the Technique.
`Thomas Iberti, Charles E. Lieber, and Ernest Benjamin
`
`LABORATORY INVESTIGATIONS
`
`Epidural Clonidine Analgesia in Obstetrics: Sheep Studies.
`james C. Eisenaeh, Maria I. Castro, David M. Dewan, andjanzes C. Rose
`
`The Enhancement of Proton/Hydroxyl Flow across Lipid Vesicles by Inhalation An-
`esthetics.
`
`Douglas E. Raine: and David S. Cafijg
`The Influence of Dextrose Administration on Neurologic Outcome after Temporal-y
`Spinal Cord [schemia in the Rabbit.
`john C. Druminond and Suzanne S. Moore
`Tachyphylaxis to Local Anesthetics Does Not Result from Reduced Drug Efi‘emveneSs
`at the Nerve Itself.
`Peter Lipfert, Holger Holihusen, a-ndjeachim O. Amdg
`Comparison of the Effects of Halothane on Skinned Myocardial Fibers from Newborn
`and Adult Rabbit. I. Eflects on Contractile Proteins.
`Elliot]. Krone andjudy Y. Su
`Regional Differences in Left Ventricular Wall Motion in the Anesthetized Dog.
`johon Diederieks, Bruce j. Leone, and Pierre Foeic
`Effects of “Nitrendipine” on Nitrous Oxide Anesthesia, Tolerance, and Physical De-
`pendence.
`S. Delin and H. Little
`
`42
`
`47
`
`5]
`
`57
`
`64
`
`71
`
`76
`
`82
`
`91
`
`MEDICAL INTELLIGENCE ARTICLE
`
`Pulse Oximetry.
`Kevin K. Treniper and Steven Barker
`
`98 /
`
`(Continued on page 7]
`
`f
`
`0004
`0004
`
`FITBIT, EX. 1017
`
`FITBIT, Ex. 1017
`
`

`

`January IEJBU—ANESTI-IESIOLOGY
`
`CONTENTS
`
`(Continued From page 5)
`
`LABORATORY REPORTS
`
`Laudanosine Does Not Displace Receptor-specific Ligands from the Benzodiazepinergic
`or Muscarinic Receptors.
`Yeshayahn Kat: and Moshe Gaoish
`
`Effects of Mathemoglobinemia on Pulse Oximetry and Mixed Venous Oximetry.
`Steven j. Barker, Kevin K. Tremper, and john Hyazz
`
`Hyperbilirubinemia Does Not Interfere with Hemoglobin Saturation Measured by Pulse
`Oximetry.
`Francis Veyekemans, Philip};
`Thierry Cterbaux
`
`E. Guillaume, Eric Willems, Annie Robert, and
`
`e Baete,
`
`Evaluation of a Blood Gas and Chemistry Monitor for Use during Surgery.
`G, Bashem, Wesley K. Greydanns, and Margaret A. Kenny
`
`A Model for Determining the Influence of Hepatic Uptake of Nondepolarizing Muscle
`Relaxants in the Pig.
`johann Month, Pin: ]. Hennis, Franz Alto Zimmermann, and Sander Agosto”
`Transtracheal Doppler: A New Procedure for Continuous Cardiac Output Measure-
`ment.
`
`jerome H. Abrams. Roland E. Weber, and Kenneth D. Holman
`
`109
`
`1 12
`
`1 18
`
`123
`
`128
`
`134
`
`CASE REPORTS
`
`Management of Acute Elevation of Intracranial Pressure during Hepatic Transplam
`
`139
`
`tation.
`
`A. W. Paulsen, T. R. Vaiek, T. H. Swygert,
`
`Treatment of Isorhythmic A-V Dissociation during General Anesthesia with Propran-
`olol.
`
`Russell F. Hit!
`
`Fiberoptic Endobronchial Intubation for Resection ofan Anterior Mediastinal Mass.
`Dir}: Younker, Randal»! Clark, and Lewis Cooet'er
`d Intravenous Caffeine Sodium Ben-
`
`1 4 l
`
`1414
`
`146
`
`-
`»
`Bolton Cratg H. Learnt, and Thom
`
`as S. Stanton
`
`(Continued on page 9)
`
`0005
`0005
`
`FITBIT, EX. 1017
`
`FITBIT, Ex. 1017
`
`

`

`January l989—-ANESTHESIOLOGY
`
`9
`
`CONTENTS
`
`.
`-
`I
`Caudal Epidural Anesthesia in an Infant With EpidermOIYSis Bunosa'
`Lawrence L. Yee, 109! 3' Gunter’ and Chad“ B. Mani”
`
`(Continued from page 7)
`149
`
`Recurrent Respiratory Depression after Alfentanil Administration.
`Rory S. jafie and Dennis Coaison
`
`Pain of Delayed Traumatic Splenic Rupture Masked by Intrapleural Lidocaine.
`Wiuiam W' Pond' Gregory M' somewme' Siong H- Thong: James A. Ranochak, and
`Gregory A. Weaver
`
`Dose-response Relationship For Succinylcholine in a Patient with Genetically Determined
`Low Plasma Cholinesterase Activity.
`Charles E. Smith, Gemini: Lewis, Francois Donati, and David R. Bevan
`
`CORRESPONDENCE
`
`Determination of Decay Constants from Time-varying Pressure Data.
`Charles Beattie, Linda S. Humphrey, and Gary Mammtmk
`Reply. Cfififird R. Swanson and William W. Muir III
`
`Use Caution when Extrapolating from a Small Sample Size to the General Population
`David J. Benefiei, Edward A. Easter, and Rodger Shepherd
`Reply. Imaa’ H. AbduE-Rasool, Daniel H. Sears, and Ronald L. [(5132
`Succinylcholine and Trismua
`Frederic A. Benny and Carl Lynch HI
`Reply. Henry Rosenberg
`An Infant Model to Facilitate Endotracheal Tube Fixation in the Pediatric ICU Patient.
`Patrick K. Birmingham and Babette Horn
`
`ve Method for Management of Accidental Dural puncture for Labor and
`An Alternati
`Delivery.
`Shae! Cohen, Jonathan S. Daiteh, and Pam! L. Gaidg'ngr
`
`High-pressure Uterine Displacement.
`Michan
`Dorsey and Waiter L. Miller
`
`Calculating the Potency of Mivacurium.
`Aaron F. Kopman
`Replyjoimj. Saoarese
`
`151
`
`154
`
`156
`
`159
`
`160
`
`150
`
`161
`161
`1 62
`
`163
`
`164
`
`165
`
`166
`
`165
`(Continued on page ] l)
`
`f
`
`0006
`0006
`
`FITBIT. EX. 1017
`
`FITBIT, Ex. 1017
`
`

`

`january 1989——A N I‘ISTI'l ESIO LOGY
`
`CONTENTS
`
`Midazolam in a Malignant Hyperthermia-susceptible Patient.
`juliana H. Brooks
`
`(Continued from page 9)
`157
`
`Exchange Autotransfusion Using the Cell Saver during Liver Transplantation.
`Marc R. Brown, Michael A. E. Ramsay, and Thomas H. Sanger:
`
`Air Entrainment Through a Multiport Injection System.
`Dean Gilbert, Theodore]. Sanford, Jr, and Brian L. Partridge
`Reply. Thelma Masada
`
`A Tracheal Tube Extension for Emergency Tracheal Reanastomosis.
`Robert S. Holzman
`
`The Relationship Between Malignant Hyperthemia and Neuroleptic Malignant Syn-
`drome.
`
`Haggai Hemesh, Dov Aizenberg, Marga Lapidot, and Hanan Munit:
`Reply. Stanley N, Carofi Stephan C. Mann, Henry Rosenberg, jg‘frey E, Fletcher, and Terry
`D. Herman-Patterson
`
`———————————_
`
`Appmpriate Facilitation of Intravenous Regional Techniques in RSD.
`Kevin Foley, Linda Schatz, and Randall L. Martin
`
`REPORT OF SCIENTIFIC MEETING
`
`ANNOUNCEMENT
`
`The Guide for Authors is published in the january and july issues. It may be found on page 33A of this
`issue.
`
`GUIDE '10 AUTHORS
`
`A NESAV ii rl mile ward (“rodent”) awn" by the Chemimi xi‘hi'l'mrl'
`
`.‘i'rt‘nfn' m id”:ri I'le journal
`
`0007
`
`FITBIT, Ex. 1017
`
`

`

`This material may be protected by Copyright law (Title 17 U.S. Code)
`
`0008
`
`FITBIT, Ex. 1017
`
`

`

`
`
`
`
`
`the extinction coefficient. equation la. If multiple solutes
`
`washout curves contained pulsations due to the arterial
`pulse in the ear. To more easily analyze the dye washout
`curve, he subtracted these pulsations from the curve, and
`in doing so he discovered that the absorbance ratio of the
`pulsations at the two wavelengths changed with arterial
`hemoglobin saturation. He soon realized that he could
`build an ear oximeter that measured arterial hemoglobin
`saturation without heating the ear by analyzing pulsatile
`light absorbancesf“ This first pulse oximeter. developed
`by Nihon Kohden, used filtered light sources similar to
`Millikan’s ear oximeter. The device was evaluated clini-
`cally in the mid 19705 and marketed with little success.2
`In the late 19705. Scott Wilber in Boulder. Colorado,
`developed the first clinically accepted pulse oximeter by
`making two modifications of
`the Nihon Kohden
`method“: First, he produced a lightweight sensor by
`using light emitting diodes (LEDs) as light sources and
`photodiodes as detectors). Consequently, the instrument
`was connected to its earciip sensor only by a small electrical
`cable. Wilber also improved the saturation estimates by
`using a digital microprocessor to store a compiex calibra-
`tion algorithm based on human volunteer data”: This
`method will be discussed in more detail below. This device
`
`Anesthesiolomf
`v 70.51:: 1.]an 1989
`
`PULSE OXIMETRY
`
`became a standard clinical and laboratory tool in pul-
`monary medicine. Although it was demonstrated to be
`accurate for intraoperative monitoring.m its size and ex-
`pense. and the cumbersome nature of the ear probe pre-
`vented its acceptance as a routine monitor. At this time.
`all oximeters produced various light source wavelengths
`by filtering white light. The filtered light was then trans
`mitted to and from the tissue through fiberoptic cables.
`In the mid 19705, Takuo Aoyagi. an engineer working
`for Nihon Kohden Corporation. made an ingenious dis~
`covery regarding oximetry. He was developing a method
`to estimate cardiac output semi-noninvasiveiy by detecting
`the washout curve of dye injected into a peripheral vein
`as it perfused the ear. This washout curve was measured
`in the ear with a red and infrared light densitometer sim-
`ilar to the Millikan ear oximeter. He noticed that his
`
`%0‘sarcoma-ray
`
`#40
`
`
`
`
`
`
`
`
`Pro. 1. This figure is from a 1951 article in Anrs'ruestolnov. It
`reveals dramatic desaturation in a 4-yr-old patient during a tonsillec-
`tomy. Reproduced from Stephen RC. Slater HM. johnson AL, Sekelj
`P: The oximeter—A technical aid for the anesthesiologist. ANESTHE—
`stotoov 12:543. 1951. with permission.
`
`The Physics and Physiology of Pulse Oximetry
`
`Bean’s Law
`
`In the 19305, Matthes used spectrophotometry to de-
`termine hemoglobin oxygen saturation.2 This method is
`based on the Beer-Lambert law, which relates the con-
`centration ofa solute to the intensity oflight transmitted
`through a solution.
`
`ltrans = line—A
`
`A = DC:
`
`(la)
`
`where 1...“, = intensity oftransmitted light; 1;" = intensity
`of incident light; A = absorption; D = distance light is
`transmitted through the liquid (path length); C = con-
`centration of solute (hemoglobin); e = extinction coeffi-
`cient of the solute (a constant for a given solute at a spec-
`ified wavelength). Thus. if a known solute is in a clear
`solution in a cuvette of known dimensions, the solute con—
`centration can be calculated from measurements of the
`incident and transmitted light intensity at a known wave-
`length. The extinction coefficient E is a property of light
`absorption for a specific substance at a specified wave-
`length. In a one-component system. the absorption A is
`the product of the path length, the concentration, and
`
`0009
`
`was developed by Biox Corporation of Boulder. Colorado,
`and was successfully marketed to pulmonary function lab-
`oratories in the early 19805.
`The clinical utility of the noninvasive oximeter in the
`operating room was rediscovered in the 1980s by William
`New, an anesthesiologist at Stanford University. Realizing
`that a continuous, noninvasive monitor of oxygenation
`would be useful to anesthesiologists, New developed and
`marketed a pulse oximeter to this group.155 The Nellcor
`model N100 had by 1985 become almost synonymous
`with the term "pulse oximeter."
`
`i Wilber 5: Blood constituent measuring device and method. US
`Patent #4. 407. 290 April 1, 1931.
`
`FITBIT, Ex. 1017
`
`

`

`K. K. TREMPER AND S.
`
`BARKER
`
`Anesthesiology
`V TD. No ].Jan 1989
`
`By the above definition of oxygen saturation, the two
`forms of hemoglobin that do not bind oxygen (COT-1b
`and MetHb) are not included. This is the origin of what
`is now referred to as “functional hemoglobin saturation,”
`defined as (Severinghausjw. personal communication);
`
`OgHb
`Functional 53.02 =m x 100%.
`
`(2)
`
`With the advent of multiwavelength oximeters that can
`measure all four species of hemoglobin, “fractional sat-
`uration” has been defined as the ratio of oxyhemoglobin
`to total hemoglobin:
`
`HEMOGLOBIN EXTINCTION CURVES
`
`Inl'rgmd
`I
`
`mathemoglobln
`
`I |
`
`oxyhemoglobin
`'IIIII.III'.--'.
`reduced
`hemoglobin
`
`
`
`ExtinctionCoefficient
`
`-__.
`carboxyhemoglobin
`
`son an:
`
`can no T60
`
`sou
`
`can
`
`so:
`
`920
`
`960
`
`moglobin saturation.”
`
`Adult blood usually contains four species of hemoglo-
`bin: oxyhemoglobin (OgHb), reduced hemoglobin (Hb),
`methemoglobin (MetHb), and carboxyhernoglobin (CO-
`Hb) (fig. 2). The last two species are in small concentra-
`tions, except in pathologic conditions. There are several
`definitions of hemoglobin saturation. Historically, “oxy-
`gen saturation" was first defined as the oxygen content
`expressed as a percentage of the oxygen capacity. The
`oxygen content (cc of oxygen per 100 cc of blood) was
`measured volumetrically by the method of Van Slyke and
`Neill (1924).15 The oxygen capacity was defined as the
`oxygen content after the blood sample had been equili-
`brated with room air (158 mmHg oxygen at sea level).
`
`Wavelength It {nm}
`
`Fractional 5302
`
`FIG. 2. Transmitted light absorbance spectra of four hemoglobin
`species: oxyhemoglobin. reduced hemoglobin, carboxyhemoglobin, and
`methcmoglobin. Adapted from Barker 5] and Trcmper KK: Pulse
`Oximetry: Applications and limitations, Advances in Oxygen Moni-
`toring. International Anesthesiology Clinics. Boston. Little. Brown and
`Company. 1987. pp. 155-175.
`
`are present, A is the sum of similar expressions for each
`solute. The extinCtion coefficient can vary dramatically
`with the wavelength of the light. The extinction coeffi-
`cients for various hemoglobin species in the red and in-
`frared wavelength range are shown in figure 2.
`Laboratory oximeters use this principle to determine
`hemoglobin concentration by measuring the intensity of
`light transmitted through a cuvette filled with a hemo-
`globin solution produced from lysed red blood cells.“1
`For Beer's law to be valid, both the solvent and the cuvette
`
`must be transparent at the wavelength used, the light path
`length must be known exactly, and no absorbing species
`can be present in the solution other than the known solute.
`It is difficult to fulfill these requirements in clinical devices;
`therefore, each instrument theoretically based on Beer’s
`law also requires empirical corrections to improve accu-
`racy.
`
`HEMOGLOBIN SATURATION DEFINITIONS
`
`02H!)
`= ——-————-—-—-— X 100 .
`0211b + Hb + COHb + MetHb
`%
`
`(3)
`
`The fractional hemoglobin saturation is also called the
`“oxyhemoglobin fraction,” or “oxyhemoglobin %.“”
`When oximetry is used to measure hemoglobin satu-
`ration, Beer‘s law must be applied to a solution containing
`four unknown species: OgHb, Hb, COHb, and MetHb.
`Expanding equation 1a to a four-component system results
`in an absorption given by:
`
`A = chlél ‘l' D2026? + D3C3€3 'l" D4C4E4.
`
`The subscripts 1 through 4 correspond to the four he-
`moglobin species. If the path lengths are the same, then
`D can be factored out:
`
`A. = D(C1€1 + 0262 'i' 0363 'l' C464).
`
`The extinction coeflicients 61 through a; are constants at
`a given wavelength 2t (fig. 2}. The absorption defined in
`equation 1c is determined from equation 1 by measuring
`the incident and transmitted light intensities. From equa-
`tion 1c, we see that four wavelengths of light are needed
`to produce four equations to solve for the unknown con-
`centrations C1 through Cd. If COHb and MetHb were
`not present, their contributions to the absorption would
`be zero and functional hemoglobin saturation could be
`determined by a two-wavelength oximeter (two equations
`and two unknowns). If two wavelengths existed for which
`the extinction coefficients for COHb and MetHb were
`
`zero, then these absorption terms would again be zero
`and a two-wavelength oximeter could measure functional
`saturation. Unfortunately, as illustrated in figure 2, the
`extinction coeflicients for GUI-lb and MetHb are not zero
`
`in the red and infrared range, and their presence will,
`therefore, contribute to the absorption. Even though the
`definition of functional hemoglobin saturation involves
`only two hemoglobin species (Osz and Hb), when
`_ MetHb and COHb are present, four wavelengths are re-
`quired to determine either functional or fractional hc~
`
`0010
`
`FITBIT, Ex. 1017
`
`

`

`Anesthesiology
`V 70. No |._]an 1989
`
`PULSE OleE‘rRr
`
`Noninvasive oximeters measure red and infrared light
`transmitted through a tissue bed, effectively using the fin—
`ger or ear as a cuvette containing hemoglobin. There are
`several technical problems in accurately estimating 52102
`by this method. First, there are many absorbers in the
`light path other than arterial hemoglobin, including skin,
`soft tissue, and venous and capillary blood. The early ox-
`imeters subtracted the tissue absorbance by compressing
`the tissue during calibration to eliminate all the blood,
`and using the absorbance of bloodless tissue as the base-
`line. These oximeters also heated the tissue to obtain a
`
`signal related to arterial blood with minimum influence
`of venous and capillary blood.
`Pulse oximeters deal with the effects of tissue and ve-
`
`_ Acsso/Dcsso
`R _
`AC‘JdO/DCQ‘H)
`
`.
`
`4
`
`)
`
`(
`
`Figure 4 is an example of a pulse oximeter calibration
`curve.“5 The actual curves used in commercial devices
`
`are based on experimental studies in human volunteers.
`Note that when the ratio of red to infrared absorbance
`
`is one, the saturation is approximately 85%. This fact has
`clinical implications to be discussed later.
`It is a fortuitous coincidence of technology and phys-
`iology that allowed the development of solid-state pulse
`oximeter sensors.“a Light emitting diodes (LEDs) are
`available over a relatively narrow range of the electro-
`magnetic spectrum. Among the available wavelengths are
`some that not only pass through skin but also are absorbed
`by both oxyhemoglobin and reduced hemoglobin. For
`best sensitivity, the difference between the ratios of the
`absorbances of OgHb and Hb at the two wavelengths
`
`nous blood absorbances in a completely different way.
`Figure 3 schematically illustrates the series of absorbers
`in a living tissue sample. At the top of the figure is the
`pulsatile or AC. component, which is attributed to the
`pulsating arterial blood. The baseline or DC component
`represents the absorbances of the tissue bed, including
`venous blood, capillary blood, and nonpulsatile arterial
`blood. The pulsatile expansion of the arteriolar bed pro-
`duces an increase in path length (see equation I b), thereby
`increasing the absorbance. All pulse oximeters assume that
`the only pulsatile absorbance between the light source
`and the photodetector is that of arterial blood. They use
`two wavelengths of light: 650 nanometers (red) and 940
`nanometers (near infrared). The pulse oximeter first de-
`termines the AC component of absorbance at each wave-
`length and divides this by the corresponding DC com-
`ponent to obtain a “pulse-added" absorbance that is in-
`dependent of the incident light intensity. it then calculates
`the ratio (R) of these pulse-added absorbances, which is
`empirically related to Sa02:
`
`Barker 5]. Boston, Little. Brown and Company, 198?. p 142.
`
`PULSI". OXIMI‘TI'RY
`
`101
`
`Absorption due to pulsatile anerial blood
`Abfiorption due to non-pulsalile arterial blood
`Absorption clue to venous and capillary blood
`Absorption clue to iISSUE
`
`LightAbsorption
`
`.
`WW“
`°° o‘o‘o’oli't’o’o’o‘o
`ALA-
`Q t. 0'O
`1. O
`7 4' 0 4.
`mom ,n,
`1‘
`A A A A A A A
`V
`O
`‘t O O O O
`’9
`Time
`
`FIG. 3. This figure schematically illustrates the light absorption
`through living tissue. Note that the AC signal is due to the pulsatile
`component of the arterial blood while the DC signal is comprised of
`all the nonpulsatile absorbers in the tissue; nonpulsatile arterial blood,
`venous and capillary blood, and all other tissues. Adapted from Ohmeda
`Pulse Oximcter Model 3700 Service Manual. 1986, p. 22.
`
`should be maximized. As we see in figure 2, at 660 nano-
`meters. reduced hemoglobin absorbs about ten times as
`much light as oxyhemoglobin. (Note that the extinction
`coefficients are plotted on a logarithmic axis.) At the in-
`frared wavelength of 940 nanometers, the absorption
`coefficient of OgHb is greater than that of Hb.
`
`Engineering Design and Physiologic Limitations
`
`Although the theory on which pulse oximetry is based
`is relatively straightforward. the application of this theory
`to the production ofa clinically useful device involves a
`
`0.4 0,6 0.8 1.01.2 1.4 1.6 1.8 2.0 2.2 2.4 2.5 2.8 3.0 3.2 3.4
`
`R =
`
`ACm/DC
`Acmroc
`
`Eco
`940
`
`FIG. 4. This isa typical pulse oximetcr calibration curve. Note that
`the Sat)E estimate is determined from the ratio (R) of the pulse-added
`red absorbence at 660 nanometers to pulse-added infrared absorbance
`at 940 nanometers. The ratios of red to infrared absorbances vary
`frotn approximately .4 at “10% saturation to 3.4 at 0% saturation.
`Note that the ratio of red to infrared absorbance is one at a saturation
`of approximately 85%. This curve can be approximately determined
`on a theoretical basis but, for accurate predictions of Sp0,. expel-i-
`mental data are required. Adapted frontjA Pologc: Pulse oximetry:
`Technical aspects of machine design, International Anesthesiology
`Clinics, Advances in Oxygen Monitoring. Edited by Tremper KK,
`
`0011
`
`FITBIT, Ex. 1017
`
`

`

`102
`
`K. K. TREMPER AND S.
`
`BARKER
`
`Anesthesiolo
`1: T0.N01.jan1989
`
`4, an absorbance ratio of one corresponds to a saturation
`of 35% on the calibration curve. PulSe oximeter error
`
`during methemoglobinemia has also been confirmed in a
`clinical report.19
`In neonatal blood, a fifth type of hemoglobin is present,
`fetal hemoglobin (HbF). HbF differs from adult Hb in
`the amino acid sequences of two of the four globin sub.
`units. Adult Hb has two oc- and two Jl9-globin chains, while
`HbF has two a: and two f chains. This difference in globin
`chains has little effect on the extinction curves and there-
`
`significant engineering effort. This section will present in
`general terms the clinical and physiologic problems of
`oximeter design and their engineering solutions. The dis-
`cussion is divided into four areas: dyshemoglobins and
`dyes, LED center wavelength variability, signal artifact
`management, and accuracy and response. The reader
`should be aware that these problems can interact with
`one another.
`
`DYSHEMOGLOBINS AND DYES
`
`Being two-wavelength devices, pulse oximeters can deal
`with only two hemoglobin species. As noted above, this
`would be adequate to measure functional Saog if MetHb
`and COHb did not absorb red or infrared light at the
`wavelengths used. Unfortunately, this is not the case, and
`therefore both MetHb and CO Hb will cause errors in the
`
`pulse oximeter reading. It is not intuitively obvious how
`a pulse oximeter will behave in the presence of dyshem-
`oglobins. With respect to carboxyhemoglobin, we can gain
`some insight from the extinction curves of figure 2. In
`the infrared range (940 nm), COHb absorbs very little
`light: whereas, in the red range (660 nm), it absorbs as
`much light as does 021‘“). This is clinically illustrated by
`the fact that patients with carboxyhemoglobinemia appear
`red. Therefore, to the pulse oximeter, COHb looks like
`021'") at 660 nm; while, at 940 nm COHb is relatively
`transparent. The effect of COHb on pulse oximeter values
`has been evaluated experimentally in dogs.” In this study,
`the pulse oximeter saturation (SpOg) was found to be given '
`approximately by:
`
`S
`
`p02
`
`:
`
`OgHb + 0.9 X COHb
`total Hb
`
`X 100%.
`
`(5)
`
`LED CENTER WAVELENGTH VARIABILITY
`
`fore should not affect pulse oximeter readings.§'ll This is
`indeed fortunate because the fraction of HbF present in
`neonatal blood is a function of gestational age and cannOt
`be accurately predicted. HbF does produce a small error
`in in vitro laboratory oximeters; OgHbF may be inter-
`preted as consisting partially of COHb.”
`The absorbance ratio R (equation 4) may be affected
`by any substance present in the pulsatile blood that absorbs
`light at 660 or 940 nm and was not present in the same
`concentration in the volunteers used to generate the cal-
`ibration curve (fig. 4). Intravenous dyes provide a good
`example of this principle.21 '22 Scheller at at. evaluated the
`effects of bolus doses of methylene blue, indigo carmine,
`and indocyanine green on pulse oximeters in human vol-
`unteers.2| They found that methylene blue caused a fall
`in SpOg to approximately 65% for 1—2 min. Indigo car~
`mine produced a very small drop in saturation, while in»
`docyanine green had an intermediate effect. The detec-
`tion of intravenous dyes by pulse oximeters should not
`be surprising. because it was this effect that led Aoyagi
`to the invention of pulse oxirnetry.2
`
`of fetal hemoglobin and bilirubin.j Perinat VII:323. 1937.
`
`The effects of methemoglobinernia on pulse oximetry
`are also partially predictable from the extinction curves
`(fig. 2). MetHb has nearly the same absorbance as reduced
`hemoglobin at 660 run, while it has a greater absorbance
`than the other hemoglobins at 940 nm. This is consistent
`with the clinical observation that methemoglobinemia
`produces very dark, brownish blood. Thus, it would be
`expected to produce a large pulsatile absorbance signal
`at both wavelengths. The effect of MetHb on pulse ox-
`imeter readings has also been measured in dogs.lg As
`methemoglobin levels increased, the pulse oximeter sat-
`uration (SpOQ) tended toward 85% and eventually became
`almost independent of the actual 53.09.18 In other words,
`in the presence of high levels of MetHb, SpOg is erro-
`neously low when SaOE is above 85%, and erroneously
`high when Saog is below 85%. This may be explained by
`the fact that MetHb causes a large pulsatile absorbance
`at both wavelengths, thereby adding to both the numer-
`ator and denominator of the absorbance ratio R (equation
`4) and forcing this ratio toward unity. As shown in figure
`
`0012
`
`The LEDs used in pulse oximeter sensors are not ideal
`monochromatic light sources; there is a narrow spectral
`range over which they emit light. The center wavelength
`of the emission spectrum varies even among diodes of the
`same type from the same manufacturer. This variation
`can be $15 nanometers.16 As seen in figure 2, a shift in
`LED center wavelength will change the measured ex-
`tinction coefficient and thus produce an error in the sat-
`uration estimate. This source wavelength effect will be
`greatest for the red (560 nm) wavelength, because the
`extinction curves have a steeper slope at this wavelength.
`Manufacturers have found two approaches