Noninvasive Oxygen Monitoring Techniques

Noninvasive Oxygen Monitoring Techniques

RESPIRATORY PROCEDURES AND MONITORING 0749--0704/95 $0.00 + .20 NONINVASIVE OXYGEN MONITORING TECHNIQUES Joyce A. Wahr, MD, and Kevin K. Tremper, P...

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RESPIRATORY PROCEDURES AND MONITORING

0749--0704/95 $0.00

+ .20

NONINVASIVE OXYGEN MONITORING TECHNIQUES Joyce A. Wahr, MD, and Kevin K. Tremper, PhD, MD

The past two decades have seen tremendous advances in noninvasive monitoring of oxygenation. In the mid-1970s, several techniques were available for investigational work, but their true utility in clinical medicine had not been demonstrated. Today, pulse oximetry is becoming the most ubiquitous noninvasive monitoring modality in medical practice. The reasons for this wide acceptance are two-fold. First, oxygen is unique in its role in mammalian survival. It must be supplied continuously to all tissues to meet the needs of consumption and it is not stored effectively. Any disruption in supply therefore quickly results in a catastrophic outcome. Secondly, the noninvasive devices that have been developed for oxygen monitoring provide continuous real-time data regarding the status of this essential substrate. Noninvasive oxygen monitoring in the critical care setting involves both monitoring of the gases delivered to the patient and monitoring of the patient's oxygenation. Each of these is discussed in turn. Noninvasive patient monitoring devices can be divided in two categories-those that measure oxygen tension (Po2 ) and those that measure hemoglobin saturation (So2 ). The two clinically available techniques for monitoring Po2 are transcutaneous oxygen monitoring (Ptco 2 ) and conjunctiva! oxygen monitoring (Pcjo2 ). The devices that measure saturation are the pulse oximeter (Spo2 ) and the tissue oximeter (near-infrared spectroscopy, NIRS). This article discusses the development and the technical, physiologic, and clinical characteristics of each of these monitoring techniques. Because the pulse oximeter is used most widely in clinical practice, it is discussed in depth.

From the Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan

CRITICAL CARE CLINICS VOLUME 11 •NUMBER l •JANUARY 1995

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CLINICAL MEASUREMENT OF OXYGEN Gas Phase

Oxygen may be monitored or measured in either the inspired or the expired concentration. Although an oxygen monitor on the inspired limb of the anesthetic or ventilator circuit does not guarantee an adequate arterial oxygen pressure (Pao 2 ), it does ensure that a hypoxic mixture is not delivered to a patient. Ideally, an oxygen analyzer should be accurate to ± 2% and capable of response within 10 seconds. It should be unaffected by relative humidity within the 30% to 90% range. Analyzer data should be compensated for both temperature and pressure, and exposure to anesthetic gases should not affect accuracy. The three commonly used monitors of inspired or expired oxygen content are the polarographic, Raman scattering, or electromagnetic techniques. Po/arographic Sensors

Electrochemical devices, or electrodes, measure a small current or voltage resulting from a chemical reaction at the sensor surface. In 1956, Leland Clark presented a small electrode that could measure oxygen partial pressure even under rapidly changing conditions. The Clark electrode is composed of a platinum cathode and silver anode 21 (Fig. 1). As with any resistive circuit, an increase in voltage increases current. This electrochemical cell exhibits a plateau, however,-for a certain range of voltages, current does not increase with voltage but does increase with oxygen tension. A polarizing potential is maintained between the anode and cathode, which are immersed in an electrolyte solution. A membrane covers one surface of the cell, through which oxygen diffuses, and the following reaction takes place at the cathode surface: (1)

Clark electrodes maintain polarizing voltages of 600 to 800 m V to obtain a stable current at each Po2 • In the laboratory setting, where all environmental conditions can be controlled, Clark electrodes are both accurate and stable. Clark's polarographic oxygen electrode has been used widely for more than 30 years and, as will be discussed in a later section, is used to measure and monitor oxygen tension in the gaseous phase, dissolved in blood, and at the tissue surface (transcutaneous or conjunctival). Polarographic sensors are the analyzers most commonly used in the inspired limb. Response times for these analyzers are about 10 to 60 seconds, not fast enough to generate respiratory waveforms. They most often are used to determine fractional inspired oxygen and fractional expired oxygen. Because the analyzer depends on a battery to operate the meter and to induce voltage on the electrode, regular preventive maintenance (replacement of electrode membrane and electrolyte gel as well as battery replacement) is essential to ensure a functional analyzer.

NONINVASIVE OXYGEN MONITORING TECHNIQUES

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B Voltage Figure 1. Schematic of a Clark polarographic oxygen electrode. A, The circuit consists of a voltage source (battery) and a current meter connecting platinum and silver electrodes. The electrodes are immersed in an electrolyte cell. A membrane permeable to oxygen but not to the electrolyte covers one surface of the cell. Oxygen diffuses through the membrane and reacts with water at the platinum cathode to produce hydroxyl ions. The ammeter measures the current produced at the cathode by the electrons consumed in this reaction. B, A plot of current produced as a function of the voltage between the two electrodes (polarizing voltage) . This plot is called a polarogram . In the range near 660 mV there is a plateau in the polarogram which occurs at higher currents as the Po2 in the cell is increased. Most polarographic oxygen electrodes use 600-800 mV polarizing voltage to obtain a stable current at each Poz.

Raman Scattering

Raman scattering is a type of absorption and re-emission phenomenon that occurs in a very small percentage of photon interactions. In this rare occurrence, light in the visible and ultraviolet range is absorbed by molecules of a substance, producing unstable vibrational or rotational energy states.34 Because these excited states are unstable, some of the absorbed energy immediately is re-emitted, allowing the molecule to relax into a stable state. These frequency shifts are species specific, and, if the intensity of the exciting light is sufficient, the Raman scattered signal can be measured and used to identify the molecules w ithin a gas

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sample. The Raman scattered light is of low intensity, so it is best measured at right angles to the high-intensity exciting beam. In addition, Raman scattering phenomena occur infrequently in any beam of light, so a high-intensity light source is required. Argon lasers currently are used as light sources for gas analyzers based on this technique. 105 Raman scattering analyzers (RASCAL, Albion Instruments, Salt Lake City, UT) are multi-agent analyzers capable of detecting and quantifying all gases encountered in the operating room. Raman systems are highly accurate, have a rapid start-up time (< 2 minutes), are unaffected by electrocautery or other operating room devices, and perform frequent self-calibrations to ensure accuracy during extended use. 104• 105 These systems are patient dedicated rather than time-shared monitors such as the mass spectrometer. Mass Spectrometers

Electromagnetic phenomena form the basis for oxygen measurement in mass spectrometers. Oersted first recognized that an electric current in a wire caused movement of a compass needle in 1820.13 Briefly, when a particle having a charge q moving at velocity v experiences a force directed perpendicular to the direction of motion, a magnetic field is present. The magnetic force is proportional to the product of the charge, q; the velocity vector v, and the induction B of the field, according to the following relationship: F = qv

x

B

(2)

The mass spectrometer is based on the principle that a moving ion of each species of gas, when exposed to a magnetic field, has a certain trajectory, based on the ratio of the charge of the ion to its mass (q/m). For a particle of charge q moving at velocity v in an electric field, E, and a magnetic induction B, the force on the particle is: F = qE + qv

x

B

(3)

The mass spectrometer first ionizes and accelerates the gas molecules by means of an electric field, E. The moving ions then pass through a magnetic field oriented perpendicular to their direction of motion. The sideways magnetic force deflects the trajectory of each type of particle through the angle, a. The deflecting force is proportional to charge q, and the sideways acceleration from this force is inversely proportional to mass m . The angle of deflection therefore is a function of q / m . This angle and the ion flux are measured by photo detectors, and the concentration of each species of gas thereby is found. The cost of mass spectroscopy is high, obviating its use as a singlepatient monitor. The development of multipatient capillary sampling systems in the early 1980s made this form of monitoring easy, reliable, and economical. 63 Because virtually every anesthesia machine has a separate oxygen analyzer attached to the inspired limb, the greatest

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usefulness of this monitor is in detection and quantification of inspired and expired carbon dioxide and inhaled anesthetic agents.

Blood and Tissue Phase

Oxygen is carried to the tissues dissolved in plasma (oxygen tension) and attached to hemoglobin (oxygen saturation). Because these two forms of oxygen are in equilibrium, oxygenation may be assessed by analyzing either the Po2 or the So2 • Hemoglobin Saturation Measurements

The earliest optical sensor used to monitor patients is one that is used unchanged to this day-the human eye. Despite its enormous usefulness, the eye is limited by its inability to monitor quantitatively. The development of the modem pulse oximeter really began in the late 1660s, when Isaac Newton came to believe that all the colors demonstrated by a prism actually existed in the beam of sunlight passing through the prism. 61 The stage thus was set for identification of the optical spectrum and, subsequently, the entire electromagnetic spectrum. Every substance having a temperature above absolute zero emits and absorbs electromagnetic radiation, and each element has a specific light emission/absorption "fingerprint". 46 Oxygenated hemoglobin absorbs less red light (600-750 nm) and more infrared light (850-1000 nm) than does deoxygenated hemoglobin (Fig. 2), for example. The specific pattern of light emission or absorption therefore can be used to identify and quantify the substances present. Pulse Oximetry. The pulse oximeter is based on the principles of light absorption. The Lambert-Beer law states that the transmission of light through a solution is a logarithmic function of the density or concentration of the absorbing molecules in the solution. The intensity of the transmitted light also is a function of the length of the path the light travels through the solution and the absorbance constant for a given absorbing particle at a given wavelength.12 This law may be written as the equation: (4)

Where Itrans = intensity of transmitted light; Iin intensity of incident light; e = natural log base (2.71828); D = distance light is transmitted through the liquid; C = concentration of the solute (hemoglobin); and al = extinction coefficient of the solute, which is a constant for a given solute at a specific light wavelength. If a known substance is dissolved in a clear solvent in a cuvette of known dimensions, therefore, the solute concentration can be calculated if the incident and transmitted light intensities are measured. Using this principle, Drabkin and Austin were able to measure the saturation of hemoglobin in a cuvette as early as 1945. 28 Laboratory oximeters use the

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Figure 2. Hemoglobin extinction curves. Transmitted light absorbance spectra of four hemoglobin species: oxyhemoglobin, reduced hemoglobin, carboxyhemoglobin, and methemoglobin. (From Pologe JA: Pulse oximetry: Technical aspects of machine design . Int Anesthesiol Clin 25:137-175, 1987; with permission.)

Lambert-Beer law to determine hemoglobin concentration by measuring the intensity of light transmitted through a hemoglobin dispersion produced from lysed red blood cells. These oximeters measure the concentration of each of the four typical species of adult hemoglobin (oxyhemoglobin, reduced hemoglobin, methemoglobin, and carboxyhemoglobin) by using a separate wavelength for each species, and writing a separate Lambert-Beer equation for each. Pulse oximeters also use the Lambert-Beer law, but with important empirical corrections. For the Lambert-Beer equation to be valid, both the solvent and the cuvette must be transparent, the length of the light path must be known exactly, and no other absorbers can be present in the solution. Obviously, these requirements could not be fulfilled in clinical application without extensive alteration. Glenn Millikan (who coined the term oximeter) presented an ear oximeter in 1941,55 but it was not capable of differentiating the hemoglobin saturation of arterial blood from that of venous blood or tissue. In 1972, Takuo Aoyagi, a Japanese engineer working on a photometric means of measuring cardiac output with dye dilution, noted that the pulsatile components of the absorbances of red and infrared light transmitted through tissue were related to arterial So2 • Application of this principle to oximeters enabled Aoyagi to build the first pulse oximeter. 5

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All currently available pulse oximeters use two wavelengths of light, one in the red band (660 nm) and one in the infrared band (most commonly 940 nm). Light emitting diodes in the probe transmit light of the appropriate wavelength through the tissue (e.g., finger, earlobe) and the intensity of the transmitted light is measured by a photo detector on the other side. As arterial blood pulses in the fingertip, the path length of light increases slightly. This increase in path length and light absorption, as shown in Figure 3, is caused solely by arterial blood in the tissue.68 The direct current (DC) component is the absorbance of the tissue bed, whereas the pulsatile arterial blood is represented by alternating current (AC). The pulse oximeter first determines the AC component of the absorbance at each wavelength and then divides it by the corresponding DC component to obtain a "pulse added" absorbance that is independent of the incident light intensity. The ratio (R) of the pulse added absorbances are related to the arterial oxygen percent saturation (Sao2): R

=

AC6w/DC66o AC940/ DC940

(5)

Pulse oximeter calibration curves, as shown in Figure 4, are developed by measuring the absorbance ratios in human volunteers while simultaneously sampling arterial blood for in vitro saturation measurements. Ratios below 70% saturation are based on empiric calculations because safety precludes gathering volunteer data at that level of hypoxia. Limitations. As already mentioned, adult hemoglobin (Hb) typically contains four species-oxygenated (02 Hb ), deoxygenated, carboxyhemoglobin (COHb), and methemoglobin. As opposed to laboratory oximeters, pulse oximeters use only two wavelengths, can measure only two Hb species, and can determine only the ratio of 0 2 Hb to Hb. As shown in Figure 1, COHb absorbs very little infrared light but absorbs as much red light as 0 2 Hb, causing patients to appear "cherry-red." To

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Time Figure 3. Schematic illustration of light transmission and absorbance through living tissue. Note that the AC signal is due to the pulsatile component of the arterial blood while the DC signal is composed of the nonpulsatile absorbers in the tissue: nonpulsatile arterial blood, venous and capillary blood , and all other tissues. (Adapted from Ohmeda Pulse Oximetry Model 3700 Service Manual , Ohmeda 1986, p 22 ; with permission.)

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0 L-..L-....l....~l--'---l'--"'--..._-'-~........__......_~..................0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2 2.4 2.6 2.8 3.0 3.2 3.4 Figure 4. Example of a pulse oximeter calibration curve. The Sa0 2 estimate is determined from the ratio (R) of the pulse-added red absorbance at 660 nm to the pulse-added infrared absorbance at 940 nm. The ratio of red to infrared absorbances varies from approximately 0.4 at 100% saturation to 3.4 at 0% saturation. The ratio of red to infrared absorbance is 1 at a saturation of approximately 85%. This curve can be approximately determined on a theoretical basis, but for accurate predictions of Spo,, experimental data are required . (From Pologe JA: Pulse oximetry: Technical aspects of machine design . Int Anesthesiol Clin 25:137-175, 1987; with permission .)

the pulse oxirneter, COHb looks like 0 2 Hb at 660 nm, whereas COHb is relatively transparent at 940 nm. In the presence of significant levels of COHb (carbon monoxide poisoning), the pulse oximeter saturation (Spo 2) is related to true saturation by the following equation8• 100 : S _ 0 2Hb + (0.9)(COHb) /c po2 total Hb x 1000 0

(6)

In dogs-with 70% COHb, the reported Spo2 was over 90%. 8 Methemoglobin (MetHb), a complication of 20% benzocaine and dapsone (an antibiotic used in malaria, leprosy, and Pneumocystis carinii4• 7• 99• 103) absorbs as much red light as reduced Hb, and more infrared light than the other Hbs, resulting in very dark, brownish colored blood. 9 Because MetHb adds significantly to both the numerator and denominator, the absorbance ratio (R) tends toward 1, resulting in a Spo2 of 85% regardless of Sao2 . In suspected cases of COHb or MetHb, an arterial sample should be sent for laboratory determination of saturation. Fetal Hb differs from adult Hb in the amino acid sequence of two of the four globin chains; these differences do not affect the extinction curves and therefore do not affect Spo2 •69 Scheller et aF6 evaluated the effects of bolus doses of various dyes in human volunteers. They found that methylene blue causes a spurious fall in Spo2, to approximately 65%, for 1 to 2 minutes. Indigo carmine produces a very small drop in saturation, whereas indocyanine green

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had an intermediate effect (brief decrease, never below 93% in the five patients tested). Clearly, methylene blue affects the pulse oximeter to the greatest degree, and, because methylene blue is used as an antidote to MetHb, the picture of a patient with MetHb who has received methylene blue is confusing. Laboratory oximeters are affected by methylene blue to a degree similar to pulse oximeters.30 Bilirubin has not been found to affect Spo2, although levels over 20 mg / dL affect laboratory oximeters.3 Onychomycosis, a superficial fungal infection of the fingernail, produces a yellowish discoloration that falsely depresses Spo2 by 3% to 5%.32 Skin pigment has been reported both to affect and not to affect pulse oximeter readings. In very darkly pigmented individuals, the readings may be erroneously high or unobtainable (3%-5%). 31 , 72 Finally, fingernail polish can affect the accuracy of Spo2 • Blue hues of polish absorb strongly close to 660 nm; black absorbs in both the red and infrared range, resulting in spurious decreases of 3% to 5%.24, 74 The light-emitting diodes (LEDs) used in pulse oximeters are not pure, but emit light over a narrow spectral range.68 A shift in the LED center wavelength will change the measured extinction coefficient and thereby produce an error in the saturation estimate, more significantly when the blood is desaturated than when it is well saturated. Incompletely compensated LED frequency variation produces probe-to-probe variability in the absolute measurement of Spo2 • Perhaps the most difficult engineering problem in pulse oximeter design is the identification of the "ripple" of arterial blood in a "sea" of electromagnetic artifact. Sources of artifact include ambient light, electrical noise, low perfusion signal, and motion. Pulse oximeters distinguish red from infrared light and both from room light by alternating the red and infrared LED light pulses hundreds of times per second with pauses to measure background light. Nonetheless, interference has been reported with fluorescent lights, 38 a xenon arc lamp, 23 infrared light, 17 and a fiberoptic cystoscope.15 Ambient light artifact is minimized most appropriately by using an opaque shield. Pulse oximeters are designed to amplify any detected pulse signal and estimate the Spo2 from the absorbance ratio; as the pulse signal is amplified (as much as one billion times), so is background noise. At the highest amplifications, a Spo2 value can be generated from noise. Most current models set minimum values for signal-to-noise ratio, but case reports exist of nonsense Spo2 values. One case report cites values generated from a heart donor after the heart was excised, and another from an open chest asystolic patient with no arterial pressure. 26 Tricuspid regurgitation and intra-aortic balloon pumps can interfere with recognition of the arterial pulse. 89, 92 If the saturation has been determined erroneously from background noise, the heart rate displayed is at variance with that determined from the electrocardiogram (ECG). Low pulse wave amplitude due to peripheral vasoconstriction (hypovolemia, hypothermia, poor cardiac output, extremes of systemic vascular resistance) is more critical to determination of Spo2 than either flow or blood pressure.2, 22, 47, 64 In two similar studies in which Spo2 was

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measured in digits with hypotension but not vasoconstriction, accurate saturation values were obtainable despite quite low mean arterial pressures (30-40 mm Hg). 33, 82 Correct Spo2 values and pulse rates have been obtained when flow through the finger is as little as 8.6% of baseline. 48 Patient motion has been shown to be the most frequent cause of failure or spurious desaturation episodes, 107 and shivering may interfere with pulse oximetry.78 Accurate Spo2 readings have been reported during tonic clonic seizures42 and during helicopter transport. 86, 94 As with amplified background noise, motion artifact is detected best by observation of the plethysmograph waveform or by comparing the heart rate with that determined by ECG. Electrocautery and magnetic resonance imaging (MRI) scanners can cause spurious decreases in Spo2 or false alarms because of wide-spectrum radio frequency emissions picked up directly by the photo diode.16, 101 Use of pulse oximetry in the MRI scanner is difficult, both because any ferromagnetic materials will interfere with imaging, and because the Spo2 accuracy in the MRI scanner appears to differ substantially among oximeter models. 78 Accuracy. As noted, there have been some 50 published studies of pulse oximetry accuracy and reliability since 1983; comprehensive reviews exist in the literature.45, 78· 95 Overall failure rates are 2% to 3% overall and 7% in the sickest patients. 56, 57 Also noted earlier, calibration curves do not include experimental data below Sao2 of 70% and clinical studies that test accuracy below 70% are rare. Available data indicate that bias and precision vary widely among manufacturers at saturations below 70%, and that precision worsens significantly at such levels.80, 81 Although reported values below 70% may be somewhat inaccurate, the average clinician is more concerned with reinstitution of appropriate oxygenation than absolute accuracy. Nose and ear probes track Sao2 with a shorter response time than finger or toe probes. Finger probe response times vary in the literature from 20 to 150 seconds, whereas ear probe response times vary from 10 to 80 seconds. 19· 80· 81, 109 Available data indicate that Spo2 underestimates Sao2 at very low hematocrit levels.79 In dogs, bias and precision were 0.2 ± 7.6% at normal levels, and worsened to - 5.4 ± 18.8% at hematocrits less than 10%.51 Complications. Pulse oximetry is noninvasive and the potential dangers associated with its use are relatively few . Other than falsepositive (reporting of hypoxia when none exists) and false-negative (failure to report hypoxia when present) readings, true complications are rare. There are several reports of severe burns underneath probes used in MRI scanners, 10· 84 " suntanning" and burns in neonates, 60· 66· 90 burns associated with defective probes,88 and pressure injury.75 These complications can be obviated with routine inspection of the digit to which the probe is applied. Applications. By far the most frequent use for the pulse oximeter is detection of hypoxemia-" the sentry standing at the cliff of desaturation."95 A vast array of studies have show n that pulse oximetry w ill detect a significant number of desaturation episodes undetected by

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trained observers.* Yet no study has demonstrated a reduction in morbidity or mortality associated with the use of pulse oximetry. A multicenter Danish study involving 20,802 patients randomly assigned to be monitored with or without pulse oximetry found no significant difference between groups in postoperative complications (including death). 45' 57 Because of the very low mortality associated with anesthesia, it is highly unlikely that pulse oximetry will ever be demonstrated to significantly decrease the incidence of death associated with anesthesia; it also is highly unlikely that anesthesiologists will ever choose to discontinue the use of such a simple, inexpensive monitor with such theoretically valuable information. It is crucial to recognize, however, that the most vital monitor in operating and recovery rooms remains a trained, vigilant anesthetist. Other applications cited include monitoring of hyperoxia in premature infants, assessment of tissue perfusion, 40, 52, 62• n, 87• 93 and assessment of circulation. 18 ' 65, 102 Near-Infrared Spectroscopy. Incident light reflected from a solute also can be analyzed to determine concentration. Reflectance spectrophotometry, such as that used in mixed venous saturation pulmonary artery catheters, is more complex than that based on absorption because the intensity of reflected light depends both on the concentration of the solute and on the depth the light penetrates (optical path length) into the solution or tissues. As shown in Figure 5, 0 2 Hb reflects more red light than does deoxygenated, whereas both species of Hb reflect infrared light similarly. 91 In 1977, Frans Jobsis described a near-infrared instrument capable of measuring the concentrations of oxygenated and deoxygenated Hb, as well as the concentration of the respiratory enzyme cytochrome oxidase (cytochrome aa3) in cerebral and myocardial tissue.43 Since that initial description, there has been tremendous interest in such a device, and there are at least 10 companies developing and manufacturing NIRS. 39 NIRS, like pulse oximetry, is based on the Lambert-Beer law of

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Figure 5. Relative reflection of Hb and Hb0 2 . Reflected light intensities of oxygenated and deoxygenated hemoglobin. (From Sperinde JM , Senelly KM: The oximetrix opticath oximetry system. In Fahey PJ (ed): Continuum of Blood Oxygen Saturation in the High Risk Patient Mountain View, California, Abbott Laboratories, 1987, p 62; with permission .)

*References 6, 14, 25, 27, 44, 49, 53, 54, 58, 67, 70, 77, 79, 106, 108.

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light absorption. Light of several near-infrared wavelengths (700-1000 nm) is transmitted into the tissue, and the amount of light reflected at each wavelength is measured. Near-infrared wavelengths are suited ideally for this application because they are transmitted easily through bone and muscle, and demonstrate characteristic absorption bands for each of the chromophores of interest. Hb02 absorbs more light than Hb above 810 nm, less light below 800, and the same at 805 nm (isobesic wavelength). Cytochrome aa3 has a broad band of absorption, between 830 and 840 nm. Limitations. Application of the Lambert-Beer law to living tissues is difficult because the optical path length cannot be determined precisely and because light is both absorbed and scattered. The means of determining optical path length accurately remains problematic in NIRS technology. Resolution of this problem is being attempted by time-offlight and absorbance and phase modulation of the light source. Evaluation of new technology most often is accomplished by comparison with existing technology. Because NIRS continuously reports information not available from any other source (cytochrome aa3 redox state and global cerebral tissue oxygenation) it will be very difficult to assess the accuracy of the information. As experience with this technology increases, however, normal and abnormal patterns will be delineated. It is hoped that this technology eventually will provide information on both regional and global cerebral oxygenation, total cerebral blood volume (by measuring changes in total Hb over time), and cerebral utilization of delivered oxygen (cytochrome redox state). Expected applications include diagnosis of injury (imaging of the brain, similar to that accomplished with MRI), monitoring of cerebral injury (closed head injury, stroke, hemorrhage), monitoring to prevent injury (during carotid endarterectomy or cardiopulmonary bypass, or fetal monitoring during second-stage labor).

Oxygen Tension Monitoring

Transcutaneous Po 2 • In 1972, two European researchers reported that Po2 values similar to Pao 2 could be obtained by heating a Clark electrode and placing it on the skin surface. 29, 41 Over the next decade, this technique, known as transcutaneous oxygen monitoring, became common in the care of premature infants at risk of hypoxia or hyperoxia. Ptco 2 is the oxygen tension of heated skin. The stratum corneum, composed of lipid in a protein matrix, normally is a very efficient barrier to gas transport but, when heated above 41°C, the structural characteristics of this layer change, allowing oxygen to diffuse readily. 11 Heating also arterializes the capillary blood. Cutaneous oxygenation depends both on the arterial oxygen content and on blood flow to the dermal vasculature. Ptco 2 decreases as cardiac output decreases, whereas Pao 2 is constant. 73 This lessens the usefulness

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of Ptco2 as a monitor of arterial oxygenation, but makes it a valuable monitor of peripheral perfusion. The effect of cardiac output on the Ptco2-Pao2 relationship can be quantified in terms of a Ptco2 index: Ptco2 index

=

Ptco2 /Pao2

Table 1 lists the ranges of the Ptco 2 index as a function of age or cardiac index. 73 The adult Ptco 2 index is 0.79 during stable hemodynamic conditions but falls to less than 0.5 when the cardiac index is less than 2.2 L/minute/m2 •98 In hemodynamically stable patients, Ptco2 index decreases progressively with age, from premature infants to elderly patients. Ptco2 index is relatively insensitive to probe location as long as it remains on the trunk. Complications. Because the skin must be heated to at least 41°C, the Ptco2 sensor will leave a red, hyperemic area wherever it is placed. This hyperemia usually disappears within 24 hours; no data in the literature relate incidence of bums to probe temperature and duration of application. In practical usage, electrode temperature usually is limited to 44°C and location is changed every 4 to 6 hours. In premature infants, the location usually is changed more frequently, and electrode temperature is somewhat less. Sensor Calibration and Drift. As with any Clark electrode, the Ptco2 electrode must be calibrated and maintained properly. The zero point (02 tension = 0 mm Hg) is extremely stable and requires calibration only once a month. The upper calibration uses room air and should be checked prior to each application. The electrodes have miniature reservoirs that bathe the electrode and the cell membranes. The reservoirs contain only 0.02 mL of electrolyte and evaporation is more of a consideration in the heated environment of the electrode than in bench-top analyzers. The reservoir and membrane should be replaced at least once a week and whenever the high calibration point drifts more than 1% in an hour. Effect of Anesthetic Agents. In 1971, Severinghaus reported that halothane is reduced at the cathode of the Clark electrode, producing a significant upward drift of Po2 . 83 This does not present a significant problem with bench-top analyzers because the amount of halothane in intermittent blood samples is limited. Ptco 2 sensors applied to the skin of patients receiving halothane, however, are exposed continually and Table 1. TRANSCUTANEOUS OXYGEN MONITORING INDEX Ptco 2 Index

Age/Hemodynamic Status

± ± ± ± ± ± ±

Premature infants Newborn Pediatric Adult, cardiac index > 2.2 Uminute/m 2 Adult, age > 65 years Adult, cardiac index 1.5-2.2 Uminute/m 2 Adult, cardiac index < 1.5 Uminute/m 2

1.14 1.0 0.84 0.8 0.7 0.5 0.1

0.1 0.1 0.1 0.1 0.1 0.1 0.1

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may show significant drift. 97 This drift has been reported as clinically insignificant (0.7 mm Hg / hour in the zero point calibration) when the Teflon membrane is 25 µ; thinner membranes (12.5 µ Teflon) show a more significant drift. 59 Sensor Location and Wann-up. Ptco2 measured on the extremities generally is lower than that measured on the chest or abdomen; even adjacent locations on the trunk can show 10% variation in reported Ptco 2 • Following placement of the electrode on the skin, approximately 8 to 10 minutes are required before the sensor will display a steady value. Under conditions of low dermal perfusion, up to 20 minutes may be required. Should the sensor become dislodged, it will report the Po2 of room air, 159 mm Hg at sea level. Finally, external pressure on the electrode will compress the dermal capillaries, producing a falsely low Ptc02. Applications. The transcutaneous analyzer has found its widest application in the neonatal intensive care unit as a monitor of hyperoxia rather than hypoxia. Retinopathy of prematurity, or retrolental fibroplasia (ROP), is associated with administration of supplemental oxygen.n° Although a wide variety of factors have been implicated in development of ROP, it often is recommended that Pao 2 be maintained below 80 to 100 mm Hg. 20 As discussed earlier, pulse oximeters' inherent inaccuracy (2%-3%) and the lack of consensus on an acceptable Spo2 make the technology less valuable in this setting. In addition, because the oxyhemoglobin dissociation curve of HbF is shifted to the left of that of HbA, the Pao2 at a given Sao2 is lower for HbF. Current recommendations include monitoring of oxygen tension, either by intermittent laboratory analysis or via Ptco2.78

Conjunctiva! Po 2 When the eyes are closed, the cornea receives its oxygen supply from the palpebral conjunctiva, whose blood supply is the ipsilateral carotid artery. Miniaturized Clark electrodes have been made to fit inside a polymethyl methacrylate ocular conformer ring, which applies the Clark electrode directly to the inner surface of the palpebral conjunctiva. 85 The electrode is not heated because there are few cell layers between the capillaries and the mucous surface. This device therefore is more nearly a true tissue oxygen monitor. This technique offers several advantages. First, because the probe is not heated, it equilibrates with local tissue Po 2 within 60 seconds. Second, Pcjo 2 reflects changes in carotid arterial oxygenation. Pcjo2 has been found to be related to cardiac output in the same manner as Ptco2, and the Pcjo2 index decreases progressively with decreasing blood volume or cardiac output, as does the Ptco2 index.1• 35 The normal Pcjo2 index is 0.6 to 0.7, with lower values in older patients. Practical limitations of conjunctival oxygen monitoring are the same as transcutaneous monitoring--electrode maintenance, calibration, and

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anesthetic (halothane) interference. Unlike Ptco 2, the Pqo2 sensor does not produce burns or require prolonged warm-up, but there is a potential for eye injury. Clinical studies to date have not reported serious eye problems.1, 35, s 5

SUMMARY

As this article demonstrates, tremendous progress has been made in the techniques of oxygen measurement and monitoring over the past 50 years. From the early developments during and after World War II, to the most recent applications of solid state and microprocessor technology today, every patient in a critical care situation will have several continuous measurements of oxygenation applied simultaneously. Information therefore is available readily to alert personnel of acute problems and to guide appropriate therapy. The majority of effort to date has been placed on measuring oxygenation of arterial or venous blood. The next generation of devices will attempt to provide information about living tissue. Unlike the devices monitoring arterial or venous oxygen content, no "gold standards" exist for tissue oxygenation, so calibration will be difficult, as will interpretation of the data provided. The application of these devices ultimately may lead to a much better understanding of how disease (and the treatment of disease) alters the utilization of oxygen by the tissues.

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Address reprint requests to Joyce A. Wahr, MD Department of Anesthesiology University of Michigan UH- 1G323, Box 0048 1500 East Medical Center Drive Ann Arbor, MI 48109-0048