System and Method of Measuring Venous Oxygen Saturation Using Intelligent Pulse Averaging With Integrated EKG and PPG Sensors

Abstract

A system using combined electrocardiography (EKG) and photoplethysmography (PPG) sensing, to determine venous oxygen saturation is described. The system uses averaging of similar pulses based on Prior (or n−1) R-to-R pulse wave duration, and current (or n) R-to-R pulse wave duration for evaluation of the metabolic reserve and/or stress of the patient.

Claims

1. A system for determining venous oxygen saturation, comprising: (a) a device positionable against a person's skin; (b) at least one PPG sensor mounted on the device for measuring the person's PPG signal at multiple wavelengths of light; (c) a plurality of electrodes for measuring the person's EKG signal; (d) a computer logic system for receiving and analyzing the PPG signal and the EKG signal, wherein the computer logic system further comprises: (i) a system for identifying cardiac cycles in the EKG signal; (ii) a system for segmenting the PPG signal into a series of PPG signal segments based upon features in the identified cardiac cycles, (iii) a system for sorting the PPG signal segments into a plurality of bins, each bin based upon durations of prior R-to-R cardiac cycles and current R-to-R cardiac cycles, (iv) a system for generating a composite signal for each of the plurality of bins, and (v) a system for measuring a person's venous oxygen saturation by: (a) calculating arterial oxygen saturation by comparing composite signals measured at different wavelengths of light, (b) sub-sampling composite signals at two consecutive signal maxima measured at different wavelengths of light, and (c) comparing the sub-sampled composite signals measured at different wavelengths of light to the calculated arterial oxygen saturation to determine venous oxygen saturation.

2. The system of claim 1, wherein calculating arterial oxygen saturation by comparing composite signals measured at different wavelengths of light comprises comparing composite Signal Prime Over Signal (SPOS) signals, each composite SPOS signal being the derivative of a composite signal normalized by the composite signal itself.

3. The system of claim 1, wherein the system for measuring a person's venous oxygen saturation selects preferred bins from which the composite signals are used when calculating the person's venous oxygen saturation.

4. The system of claim 3, wherein the preferred bins correspond to the bins having the largest number of PPG signal segments therein.

5. The system of claim 4, wherein the preferred bins correspond to the bins having the largest difference between current and prior R-to-R values.

6. The system of claim 1, wherein the system for generating a composite signal for each bin comprises a system for summing or averaging the PPG signal segments in the bin.

7. The system of claim 6, wherein the composite signal is used to generate a composite Signal Prime Over Signal (SPOS) which is the derivative of the composite signal normalized by the composite signal itself.

8. The system of claim 7, wherein the computer logic system further comprises: (vi) a system for calculating arterial oxygen saturation by comparing composite SPOS signals measured at different wavelengths of light.

9. The system of claim 1, wherein the system for generating a composite signal for each of the plurality of bins comprises a system for removing aberrant PPG signal segments from the calculation of the composite signal.

10. The system of claim 9, wherein the system for removing aberrant PPG signal segments from the calculation of the composite signal comprises a system for iteratively re-calculating the composite signal, by: comparing a SPOS of each of the PPG signal segments used to calculate a composite signal against the SPOS of the calculated composite signal, removing outlier PPG signal segments, re-calculating the composite signal with the outlier PPG signal segments removed, and repeating the iteration until there are no more outlier PPG signal segments.

11. The system of claim 1, wherein the device is a hand-held device with the at least one PPG sensor mounted thereon and a plurality of electrode wires extending therefrom.

12. The system of claim 11, wherein the device is a hand-held device with the at least one PPG sensor mounted thereon and at least one of the plurality of electrodes mounted thereon.

13. The system of claim 11, wherein an optical waveguide is interposed between the at least one PPG sensor on the device and the person's skin.

14. The system of claim 1, wherein the device is positioned within a strap or band disposed around the person's chest or limb such that the at least one PPG sensor and the plurality of electrodes are disposed within the strap or band disposed around the person's chest or limb.

15. The system of claim 1, wherein the device is a patch with the at least one PPG sensor and at least one of the plurality of electrodes positioned therein.

16. The system of claim 1, wherein the computer logic system is positioned within the device such that the composite signals are generated within the device, and wherein the system for measuring venous oxygen saturation comprises: a data transmission system for transmitting one or both of: the composite signals to a remote computer system for analysis, or measured PPG and EKG signals to a remote computer system for analysis.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0034] FIG. 1 is a top-level flow diagram of the operation of the present system.

[0035] FIG. 2 shows a PPG signal filtered through a “tissue sandwich”, showing slight changes at the end of the pulse.

[0036] FIG. 3A is an illustration of LED sampling for standard PPG arterial hemoglobin oximetry.

[0037] FIG. 3B is an illustration of end-pulse/signal maxima sampling.

[0038] FIG. 4A illustrates arteriole/capillary/venule structure is shown as an hourglass.

[0039] FIG. 4B corresponds to FIG. 4A, with the structure measured in reflective oximetry.

[0040] FIG. 5A illustrates LED sampling through the structure of FIGS. 4A and 4B at end-pulse/signal maxima before and after long pulses.

[0041] FIG. 5B illustrates LED sampling through the structure of FIGS. 4A and 4B at end-pulse/signal maxima before and after short pulses.

[0042] FIG. 6 shows the process of R-wave peak refinement used to generate t0n.

[0043] FIG. 7 shows the nomenclature and data structures used in the description of the present system.

[0044] FIG. 8 also shows the nomenclature and data structures used in the description of the present system.

[0045] FIG. 9 is an exemplary illustration of various physical components of the present system.

[0046] FIGS. 10A to 10D show various views of a hand-held embodiment of the present system, having PPG and EKG sensors mounted thereon or attached thereto.

[0047] FIG. 11 is a is a cut-away view of a portion of the device of FIGS. 10A to 10D, showing an optical waveguide adjacent to a PPG sensor.

[0048] FIG. 12A is an illustration of the system of FIGS. 10A to 11 collecting PPG signals from a person's fingers.

[0049] FIG. 12B is an illustration of the system of FIGS. 10A to 11 collecting PPG signals from the outside of a person's arm.

[0050] FIG. 13 is a is an illustration of EKG and PPG signals measured over time and generated SPOS signals corresponding thereto.

[0051] FIG. 14 is a is an illustration of one-sided Gaussian fitting.

[0052] FIG. 15 illustrates the time relationship of the end-pulse/pre-pulse area of interest relative to the SPOS negative spike fitting window.

[0053] FIG. 16 illustrates a time-correlated comparison of EKG and PPG signals showing the relationships in creation of two-beat dependencies, showing current and prior “R-to-R”.

[0054] FIG. 17A illustrates the number of pulses in each bin for a run of a patient with normal sinus rhythm.

[0055] FIG. 17B illustrates filling of the Current R-to-R versus Prior R-to-R matrix for purposes of determining end-pulse oximetry (the greatest difference in R-to-R duration), and the “fall-back” or second tier bin choices using intermediate bins providing PPG signal maxima differences allowing for venous oxygen saturation estimation.

[0056] FIG. 18 is a top-level block diagram for the end-pulse/venous oxygen saturation calculation.

[0057] FIG. 19 is a is an exemplary algorithm for preparing Pulse Data Sets in accordance with the present system.

[0058] FIG. 20 illustrates the derivation of the Pulse Wave Transit Time (PWTT).

[0059] FIG. 21 shows the calculation of end-pulse/venous oxygen saturation.

[0060] FIG. 22 illustrates an exemplary embodiment of the present system disposed in a chest strap.

[0061] FIG. 23 is a is a sectional view through the patient corresponding to FIG. 22.

[0062] FIG. 24 illustrates an exemplary embodiment of the present system incorporating a bicep strap with an electrode extending therefrom.

[0063] FIG. 25 is a is a sectional view through the patient corresponding to FIG. 24.

DETAILED DESCRIPTION OF THE INVENTION

[0064] The central element of the system is the identification and manipulation of PPG signals on the basis of Prior R-to-R and Current R-to-R duration. The system them generates composite pulses from similar pulses.

[0065] In accordance with preferred aspects disclosed in U.S. Provisional patent application 62/955,196, entitled A System For Synchronizing Different Devices To A Cardiac Cycle, filed Dec. 30, 2019 and in U.S. patent application Ser. No. 17/135,936, entitled SYSTEMS FOR SYNCHRONIZING DIFFERENT DEVICES TO A CARDIAC CYCLE AND FOR GENERATING PULSE WAVEFORMS FROM SYNCHRONIZED ECG AND PPG SYSTEMS, filed Dec. 28, 2020, incorporated herein by reference in their entireties, the present system uses a specific trigger to set time=0 for each beat (e.g. EKG R-wave peak) and then stores each pulse from this start point until completing a full cycle of sensor data, such as with LED oximetry signals from maximum to minimum and back to maximum—which will be a waveform longer than a single pulse length. The next pulse waveform will have a t=0 at the next EKG R-wave peak, thus recording of the next beat will start before the recording of the last pulse waveform has completed. In absolute terms, the time corresponding to t=0 for the nth pulse will be referred to as time t0n throughout the rest of the specification.

[0066] FIG. 6 shows the process of R-wave peak refinement used to generate t0n. The example shows how the algorithm has determined the polarity of this collection to be negative (wires reversed), and thus the R-wave to be negative. The t0n of the R-wave peak is found using polynomial fitting (602) to EKG datapoints (601) and interpolation, then used to define a Pulse Data Set.

[0067] FIG. 7 and FIG. 8 show the nomenclature and data structures used in the description (Unless otherwise specified, PWTT=PWTTIR and PPG signal=PPG signalIR). The t0n time point is then used to define a Pulse Data Set with the PPG signals of multiple wavelengths (here red, infrared, and green). Stored with the PPG signal are the values for the prior R-to-R, and current R-to-R durations, the derived signals for Signal Prime over Signal (SPOS) for each wavelength, and the Pulse Wave Transit Time (PWTT) for each wavelength. Note the first PPG signal maxima (701) and the second PPG signal maxima (702). FIG. 8 shows the structure of the Composite Pulse Data Set, constructed from a group of Pulse Data Sets on the basis of a defined criteria (e.g. similar prior R-to-R, or current R-to-R duration). Note how the PPG waveforms are of duration longer than a single cardiac cycle, and are long enough to assure capture of both the first (801) and second PPG signal maxima (802).

[0068] FIGS. 9-11 show a preferred device implementation of the system. The device block diagram shows the elements of the device/system, with multiple wavelength LEDs (901) and a photodiode detector (902), and EKG input from electrodes (903) applied to the left and right chest (or left and right upper extremities. In preferred embodiments, signals are then fed to a processing unit (904) carrying out “on-chip” logic that then generates Composite Pulse Data Sets from raw signal. The Composite Pulse Data Sets are then communicated via either wireless or direct cable connection to an “off-device” display/computing unit (905) that provides the user with the final end-pulse oxygenation, arterial main-pulse oxygenation, and resulting venous saturation estimation with more graphical options (such as changes over time). There is also on-device storage (906) for code as well as buffering and packetized transfer of data. In an alternate embodiment, the processing unit simply coordinates communication of raw ECG and PPG signal data to the external computing/display device which handles all aspects of the hydration level estimation logic. In yet another embodiment, all aspects of hydration level estimation are carried out by the processing unit, including rendering of graphics and reporting of oxygen saturation. In this case, the external computing/display device provides only the display function.

[0069] FIGS. 10A-D show various view of the PPG collection device. 1001 shows the optical waveguide (in front of LEDs and detector); 1002 shows optional incorporated EKG electrodes; 1003 shows plug-in connector sites for EKG lead wires to adhesive EKG electrodes (on right and left chest).

[0070] FIG. 11 shows detail of the PPG head, with an optical waveguide (1101) that abuts the LEDs and detector (1102) on the interior of the device. The optical waveguide allows for collection of PPG signals at sites other than the finger.

[0071] FIGS. 12A and 12B depict the device in use collecting PPG signals from the finger (FIG. 12A), and the outside of the upper arm (FIG. 12B). The PPG measurement end of the device is applied to the skin in a stable fashion so that PPG measurement can be taken over the course of 1-2 minutes or more. EKG electrodes are applied to the left and right sides of the torso (or upper extremities) and connected to the plug-ins on the smaller end of the device.

[0072] Returning to FIG. 1, PPG and EKG signals are collected. PPG waveform selection is performed to screen out aberrant beats considerably different than the majority of pulses, such as premature ventricular contraction beats, an example where the cardiac contraction does change appreciably from the beat prior.

[0073] FIG. 13 shows: EKG signal (1301); EKG R-wave peak (1302); PPG signal segments (contained within Pulse Data Sets) (1303, 1304, 1305); SPOS signals (contained within Pulse Data Sets) (1306, 1307, 1308); PWTT using SPOS (also contained within Pulse Data Sets) (1309, 1310, 1311). This demonstrates selection of one of the PPG signals (in the current implementation red, infrared, and green are used, though the approach is not limited to using these alone) with full time length for both PPG signal and SPOS longer than the R-to-R duration.

[0074] The present method and system of intelligent pulse averaging counters the effect of drift in “K” (seen in equation 1), related to absorption from fixed elements in the tissue being analyzed. With averaging, some pulses will have an upward drift in K, some will have a downward drift, leaving the averaged pulse with more options for data point comparisons across the composite pulse width.

[0075] SPOS generates similar shaped curves for the LED signals for the different wavelengths, magnitude differing only by a multiplier that is the Σ(α*Hb) for the specific wavelength. The present system includes the two novel approaches of examining the SPOS signal in the region of the “negative spike” to determine: [0076] the linearity of the rising LED SPOS signal, or [0077] the fit of the SPOS signal to a combination of Gaussian derivatives and/or exponential and/or polynomial equations.

[0078] Given the similar shapes for the SPOS curves, any such fitting can be applied to one wavelength to yield a fitted curve. Fitting to another wavelength only requires finding the magnitude needed to best fit that curve. For example, if f(t) best fits the infrared LED SPOS, then “A” needed to best fit A*f(t) to the SPOS for the red LED signal yields the arterial oxygen saturation just as with the equation 1. The difference with the standard formulation is that this fitting is based on many more time points (up to 50 at slower heart rates) than the two (maximum and minimum) used in the standard formulation.

[0079] FIG. 14 shows this concept using a one-sided Gaussian derivative fitting. Curve 1401 are the datapoints of a collected Composite IR SPOS signal with a fitting window 1402 selecting out the negative SPOS “spike”. Curve 1403 shows the datapoints for the window in an expanded plot, also showing the one-sided Gaussian derivative fitted curve 1404.

[0080] The interval of the fitting window selected (the SPOS “negative spike”), or subset thereof (e.g. the rising SPOS right half of the “negative spike”) represents a unique period wherein a single dominant and coherent physiologic event—the contraction of the left ventricle during the time of an open aortic valve—is clearly separate from other confounding physiologic features. This allows for extraction of parameters, which can then be applied to the entire PPG sensor pulse waveform.

[0081] The interval just preceding this fitting window for the “negative spike” of the SPOS represents yet another unique interval, as described in the summary of the physiology above. FIG. 15 shows the time relationship of the end-pulse/pre-pulse area of interest relative to the SPOS negative spike fitting window. Time 1501 identifies the end-pulse point; region 1502 shows the excess SPOS PPG above expected linear or exponential “rolloff” (the shaded region of FIG. 15 corresponds to the shaded region of FIG. 2). Region 1503 identifies the window of the negative SPOS “spike” used to estimate arterial hemoglobin oxygen saturation fraction

Two Beat Complex Creation for Venous Saturation Analysis:

[0082] 2-beat complex selection for a longer train of pulses in atrial fibrillation (yielding random R-to-R duration) is shown in FIG. 16. Signal from a two-electrode, single lead EKG (curve 1601) is plotted in temporal alignment with an infrared (IR) LED PPG signal (curve 1602). As the infrared wavelength has relatively equivalent absorption from venous and arterial blood, this is the wavelength shown and used to select pulses for further analysis.

[0083] With accumulation of similar 2-beat complexes (based on similar n−1 R-to-R and n R-to-R duration), composite pulse construction can be taken from one pulse minima/signal maxima all the way through to the next pulse minima/signal maxima. With this formulation, pulse minima/signal maxima at the start of the pulse and at the end of the pulse can be compared, with additional information available regarding the cardiovascular state of the individual. FIG. 16 shows the top/bottom alignment of EKG (1601) and PPG signals (1602) showing the steps in the of generation of a composite PPG wave for purposes of venous oxygen saturation derivation.

[0084] The above EKG (1601) signal shows a series of pulses labeled A through I. Each of these pulses has a different duration, though some are closer in duration than others. 2-beat dependency ties together two successive beats, with key features being the R-to-R duration of the first beat, and the PPG signal of the second beat. This is a dependency (1603) as depicted in the bracket tying together the R-to-R duration of beat “B” (1604) and the PPG signal (1605) of beat “C”. Additionally important in this analysis is the current R-to-R duration, which for this complex is the R-to-R duration of pulse “C” (1606). Notable with the bracketed complex 1603 is a paring of a long n−1 R-to-R followed by a short n R-to-R.

[0085] Pulses B and C are analyzed together, with the R-to-R duration of B and R-to-R duration of C putting this 2-beat complex in the long n−1 R-to-R/short n R-to-R “bin”. Next, pulses C and D are considered together, with the R-to-R duration of C and R-to-R duration of D putting this 2-beat complex in the short n−1 R-to-R/long n R-to-R “bin”. Next, pulses D and E are considered together, with the R-to-R duration of D and R-to-R duration of E putting this 2-beat complex in the long n−1 R-to-R/intermediate n R-to-R “bin”. Next, pulses E and F are considered together, with the R-to-R duration of E and R-to-R duration of F putting this 2-beat complex in the intermediate n−1 R-to-R/short n R-to-R “bin”. Next, pulses F and G are considered together, with the R-to-R duration of F and R-to-R duration of G putting this 2-beat complex in the short n−1 R-to-R/long n R-to-R “bin”. Next, pulses G and H are considered together, with the R-to-R duration of G and R-to-R duration of H putting this 2-beat complex in the long n−1 R-to-R/intermediate n R-to-R “bin”.

[0086] As this analysis reveals, atrial fibrillation provides a wide range of permutations of n−1 R-to-R and n R-to-R duration. This allows for analysis using short-long and long-short n−1 and n R-to-R durations, the combinations that reveals the biggest changes in PPG signal maxima. However, with normal sinus rhythm, it is harder to select combinations that will help reveal signal maxima differences. FIG. 17A shows the number of pulses in each bin for a run of a patient with normal sinus rhythm. Note how the diagonal corresponding to the same n−1 and n R-to-R durations are most populated and the short-long and long-short bins are the least populated. FIG. 17B shows the preferential filling of the Current R-to-R versus Prior R-to-R matrix (1701) for purposes of determining end-pulse oximetry (the greatest difference in R-to-R duration), and the “fall-back” or second tier bin choices using intermediate bins (1702) providing PPG signal maxima differences allowing for venous oxygen saturation estimation.

Measuring Venous Oxygen Saturation

[0087] Because these 2-beat complexes define both the beginning and ending composite PPG signal, both first and second signal maxima (pulse minima) are therefore defined. And because accumulation of similar 2-beat complexes reduce the effect of DC drift, the methods described here also allow for an estimate of venous saturation. The top-level block diagram for the end-pulse/venous oxygen saturation calculation is seen in FIG. 18.

[0088] R-wave peak refinement of pulse “n” is done with curve fitting and interpolation (1801) prior to determining the prior (n−1) and current (n) R-to-R duration; then prior (n−1) and current (n) R-to-R durations for Pulse Data Set “n” are incorporated into Pulse Data Set “n” (1802). PPG signals are gathered, and a process of outlier rejection is carried out (including but not limited to data determined to be corrupted using accelerometer input, as well as cross-checking with multiple LED PPG sensors, 1803). Once the PPG signals of the current Pulse Data Set have been selected, the Pulse Data Set is considered together with all available prior Pulse Data Sets and their PPG signals (each of which is associated with a prior (n−1) R-to-R duration and current (n) R-to-R duration).

[0089] Available Pulse Data Sets are then sorted into a 3 by 3 bin matrix of Prior R-to-R and Current R-to-R, each of which are considered and deemed to be short, intermediate, or long duration (1804). Dynamic boundary adjustment is used to ensure relatively equal numbers across bins, to the extent possible: normal sinus rhythm yields few Pulse Data Sets available for bins off the diagonal of short-short, intermediate-intermediate, and long-long (see FIG. 17). After all Pulse Data Sets are allocated into bins, the optimal bins are selected, e.g. those bins containing the largest number of Pulse Data Sets and those that reveal the biggest changes in signal maxima (1805). With the optimal bins established, and initial Composite Pulse Data Set is formed by adding together the corresponding PPG signals of each wavelength for each Pulse Data Set in the bin (1808).

[0090] With the Pulse Data Sets in a bin and the initial Composite Pulse Data Set in hand, a pruning loop is carried out for each bin to weed out Pulse Data Sets with noisy or otherwise aberrant PPG signals (1806) that made it through the coarser outlier rejection. For each Pulse Data Set in the bin, and for each wavelength in the Pulse Data Set, the PWTT for the wavelength is compared against the PWTT for the wavelength for the Composite Pulse Data Set (aggregate of all the pulses). If the PWTT of two of the current three wavelengths (red, green, IR) are within 15% of the PWTT of the Composite Pulse Data Set, the Pulse Data Set is left in the composite. If not, the Pulse Data Set is rejected (“pruned”) and the process is run again with the remaining Pulse Data Sets. A pruned Pulse Data Set is removed from the bin and subtracted from the Composite Pulse Data Set. If the number of Pulse Data Sets falls below a specified threshold for the number in the bin (good results have been obtained with numbers down to 4), then an additional Pulse Data Set is added prior to reporting any results. The algorithm is seen in FIG. 19. FIG. 20 shows the derivation of the Pulse Wave Transit Time (PWTT). This is done using the Signal Prime Over Signal (SPOS(t)) curve for each wavelength PPG signal(t), together with interpolation and (negative) peak refinement.

[0091] The calculation of end-pulse/venous oxygen saturation then proceeds as shown in FIG. 21. The venous oxygen saturation calculation follows the derivation shown in Appendix B using 2-point composite signals composed of PPG signal maxima corresponding to incongruent R-to-R duration from 2-beat complexes (1807). The results are averaged and the venous fractional oxygen saturation is reported (1809).

[0092] System Operation:

[0093] Operational alternative options are presented in the various exemplary embodiments of the present system, below. It is to be understood that the present system can be embodied in any of the systems described herein, and that the present system is not limited solely to the various exemplary embodiments described below:

[0094] FIG. 22 illustrates use of a chest strap (2201) across the chest, with incorporated electrodes (2202) contacting the left and right chest, and LED device with detector (2203).

[0095] FIG. 23 illustrates cross section of a chest strap (2301) across the chest, with incorporated electrodes (2302) contacting the left and right chest, and LED device with detector (2303).

[0096] FIG. 24 illustrates use of a bicep strap (2401), with incorporated electrode (2402) and LED device with detector (2403). A second electrode piggybacks off existing telemetry wiring (2404).

[0097] FIG. 25 illustrates cross section of a bicep strap (2501), with incorporated electrode (2502) and LED device with detector (2503). A second electrode piggybacks off existing telemetry wiring (2504).

[0098] An advantage of a chest or arm strap or band is that the band/strap provides a normal force on the LED of the PPG sensor to get a good signal off the chest wall. In aspects where a chest or arm strap is used, optional “traction” may also be provided on the inside of the strap, similar to the silicone/adhesive bead that is found on the inside of standard bike shorts to keep the legs from riding up.

APPENDIX A: CARDIOVASCULAR PHYSIOLOGY BACKGROUND

[0099] In normal health, delivery of oxygen and glucose to tissues is adequate for tissues to meet their energy needs by aerobic glycolysis, a process using oxygen to breakdown glucose that releases far more energy than anaerobic glycolysis, or fermentation (metabolism of glucose without oxygen). Whereas aerobic glycolysis breaks down glucose to water and carbon dioxide, anaerobic glycolysis breaks the glucose down to lactic acid. In health lactate is low, and pH (affected by the presence of lactic acid) is maintained around 7.4. Anaerobic metabolism with production of lactic acid allows muscles to transiently access extra energy when the tissue needs are high and there is insufficient delivery of oxygen to “burn” the available glucose (such a situation seen when sprinting at maximal effort for short distances). The lactate thus produced is then cleared from the blood stream by the liver and converted back to glucose once the physiologic stress is resolved. This allows for complete aerobic glycolysis of the previously fermented glucose.

[0100] However, when that physiologic stress is sustained rather than transient, many things begin to go awry. This can happen when infection causes the metabolism to drastically increase; or it can happen when delivery capability is suddenly reduced, as with a heart attack; it can also happen in the setting of otherwise moderate stress in the setting of baseline reduction in heart pump function. In all cases, the oxygen requirements of the tissues increase relative to what the cardiovascular system can deliver. Oxygen obtained in the lungs cannot fully replace the oxygen removed from the blood stream in the capillaries. In this situation the arterial hemoglobin oxygenation will fall—though the venous saturation will fall even more due to the body eating into the oxygen reserve in the venous blood stored up prior to the stress (oxygen saturation of venous blood may exceed 80% in unstressed normal health). All of which yields a growing difference between arterial and venous oxygen.

[0101] As venous oxygenation falls further, lactate levels will eventually begin to rise, though recent studies have shown that the rising in lactate is preceded by a measurable fall in venous oxygenation, which that fall providing clinically useful information. To measure the venous blood oxygen, though, requires a venous blood gas sample. This is obtained by a blood draw that is immediately placed on ice and sent to a qualified lab. All of which is a relatively expensive and invasive procedure with a minimum turn-around time of around 10-15 minutes, if done STAT.

[0102] Circulatory shock causes inadequate oxygen delivery, resulting in mitochondrial hypoxia. With failure of mitochondrial oxidative phosphorylation, energy metabolism becomes dependent on anaerobic glycolysis. Anaerobic glycolysis sharply increases the production of cellular lactate, and then blood levels. With severe infection, the blood lactate concentration varies in proportion to the ongoing deficit in tissue oxygenation. The ability of the patient to clear blood lactate indicates restoration of oxygen delivery with resuscitation. Studies have shown that a lactate clearance of 10% or more predicts survival from septic shock.

[0103] Studies have also shown that falling venous oxygen can provide earlier usable information than rising lactate. This unfortunately requiring ongoing invasive monitoring via a central venous line (or Swan-Ganz intracardiac catheter) and/or repeated blood draws.

APPENDIX B: VENOUS HEMOGLOBIN SATURATION CALCULATION

[0104] At the pulse minima (LED signal maxima),

Signal.sub.max=K*I.sub.O*e.sup.[−(α*thickness).sup.connectivetissue.sup.]*e.sup.[−(staticarterialblood)*Σ(α*Hb).sup.arterial.sup.]  (1)

Signal=K*e.sup.[−ArterialPulse(t)*Σ(α*Hb).sup.arterial.sup.]*e.sup.[−VenousPulse(t)*Σ(α*Hb).sup.venous.sup.]  (2)

[0105] where (α*Hb).sub.arterial and (α*Hb).sub.venous are the absorption coefficients of the type of hemoglobin (deoxyhemoglobin, oxyhemoglobin, carboxyhemoglobin, methemoglobin), and Σ(α*Hb).sub.arterial and Σ(α*Hb).sub.venous are summations of absorption coefficient for each type of hemoglobin times the fraction of each type of hemoglobin making up the arterial and venous pulses (as they have different compositions, the arterial blood carrying a much higher fraction of oxygenated blood).

[0106] Collecting the LED signal maxima (A and B, separated in time by R-to-R duration), treating them as the time varying signal, and reordering the equation:

Signal.sub.max(t)=K*I.sub.O*e.sup.[−(α*thickness).sup.connectivetissue.sup.]*e.sup.[−(staticarterialblood)*Σ(α*Hb).sup.arterial.sup.]*e.sup.[−(dynamicarterialblood)*Σ(α*Hb).sup.arterial.sup.]*e.sup.[−(venous(t))*Σ(α*Hb).sup.venous.sup.]  (3)

[0107] With arteriole blood priming an “hour glass” structure consisting of the arterioles, capillaries, and venules toward the end of the pulse, some change in the composition of the blood toward the end of the pulse is present. This suggests that a re-evaluation of the assumption of flat venous blood profile can be done by using the following to model the change in blood composition at PPG signal maxima:

delta arterial blood=gamma*delta volume  (4)

delta venous blood=(1−gamma)*delta volume  (5)

[0108] Where gamma is somewhere between 1 and 0.5.

[00007]$\begin{array}{cc}{\mathrm{Signal}}_{\max }\left(t\right)=K_v*e^{\left[-\left(\left(1-\mathrm{gamma}\right)*\mathrm{volume}\left(t\right)\right)*.Math.{\left(\alpha *\mathrm{Hb}\right)}_{\mathrm{arterial}}\right]}*e^{\left[-\left(\mathrm{gamma}*\mathrm{volume}\left(t\right)\right)*.Math.{\left(\alpha *\mathrm{Hb}\right)}_{\mathrm{venous}}\right]}& \left(6\right)\\ 2\mathrm{ptS}POS\left({\mathrm{Signal}}_{\max }\left(t\right)\right)=-\left(\frac{B-A}{R-\mathrm{to}-R}\right)*\left(\frac{2}{B+A}\right)& \left(7\right)\\ 2\mathrm{ptS}POS\left({\mathrm{Signal}}_{\max }\right)=-\left(\frac{\mathrm{dVolume}\left(t\right)}{2*\mathrm{dt}}\right)*\left[\mathrm{gamma}*.Math.{\left(\alpha *\mathrm{Hb}\right)}_{\mathrm{arterial}}+\left(1-\mathrm{gamma}\right)*.Math.{\left(\alpha *\mathrm{Hb}\right)}_{\mathrm{venous}}\right]& \left(8\right)\\ 2\mathrm{ptS}POS\left({\mathrm{Signal}}_{\max }\right)/\left[\mathrm{gamma}*.Math.{\left(\alpha *\mathrm{Hb}\right)}_{\mathrm{arterial}}+\left(1-\mathrm{gamma}\right)*.Math.{\left(\alpha *\mathrm{Hb}\right)}_{\mathrm{venous}}\right]=-\left(\frac{\mathrm{dVolume}\left(t\right)}{2*\mathrm{dt}}\right)& \left(9\right)\end{array}$

[0109] Once again assuming that there is only deoxyhemoglobin (Hb) and oxyhemoglobin (HbO2),

[00008]$\begin{array}{cc}\frac{2\mathrm{ptS}POS\left({\mathrm{Signal}}_{\max }\left(t\right)\right)}{\begin{array}{c}[\mathrm{gamma}*.Math.{\left(\alpha *\mathrm{Hb}\right)}_{\mathrm{arterial}}+\\ \left(1-\mathrm{gamma}\right)*\left({\alpha }_{\mathrm{Hb}}+\left({\alpha }_{{\mathrm{HbO}}_2}-{\alpha }_{\mathrm{Hb}}\right)*{\mathrm{HbO}}_2\right)]\end{array}}=-\left(\frac{\mathrm{dVolume}\left(t\right)}{2*\mathrm{dt}}\right)& \left(10\right)\end{array}$

[0110] Done at two or more different wavelengths (e.g. red, infrared, though not exclusive to these), one can solve for HbO2, given that the only unknowns are HbO2 and dVolume(t)/dt. Note that Σ(α*Hb).sub.arterial at each wavelength is known from analyses done elsewhere in the system description.

[00009]$\begin{array}{cc}\mathrm{With}R=\frac{\left(2\mathrm{ptS}POS\left({\mathrm{Signal}}_{\mathrm{maxRed}}\left(t\right)\right)\right)}{\left(2\mathrm{ptS}POS\left({\mathrm{Signal}}_{\mathrm{maxIR}}\left(t\right)\right)\right)}& \left(11\right)\\ {\mathrm{HbO}}_2=\frac{\begin{array}{c}\left(1-\mathrm{gamma}\right)*\left[-{\alpha }_{{\mathrm{IR}}_{\mathrm{Hb}}}*R-{\alpha }_{{\mathrm{Red}}_{\mathrm{Hb}}}\right]+\\ \mathrm{gamma}*\left[-.Math.{\left(\alpha *\mathrm{Hb}\right)}_{\mathrm{arterialIR}}*R+.Math.{\left(\alpha *\mathrm{Hb}\right)}_{\mathrm{arterialRed}}\right]\end{array}}{\left(1-\mathrm{gamma}\right)\left[R*\left({\alpha }_{{\mathrm{IR}}_{{\mathrm{HbO}}_2}}-{\alpha }_{{\mathrm{IR}}_{\mathrm{Hb}}}\right)+\left({\alpha }_{{\mathrm{Red}}_{\mathrm{Hb}}}-{\alpha }_{{\mathrm{Red}}_{{\mathrm{HbO}}_2}}\right)\right]}& \left(12\right)\end{array}$