Home

@?igllalgiill —

1. 454 097 Sheet 7 of 11 5 404 885 Apr 11 1995 U S Patent 100 bY ASZ Olu TWNINYSL 31 09 09 AG IZ IA Mses 134 09 110 svig ag2 224 28 lt i Gly CY 139440 T AS 2 oy an gen ely 9Y F aL bu s A 9NINYOM 8 1 cu 00 gy 14 4 pd EN Sheet 8 of 11 5 404 885 Apr 11 1995 U S Patent 4e Old IYNLYIA 1 H l A2I 49 Adel 019 p 4 3889 084 0 U S Patent Apr 11 1995 Sheet 9 of 11 5 404 885 1 25 0 50 Veo 0 00 0 25 te F 1G 34 TIME 3 1 25 0 50 oo2 0 00 FIG 36 CO2 CONCENTRATION OR EQUIVALENT C02 SENSOR RESPONSE UTY CYCLE ETCO2 ETCO2 1002 ETCO2 l 2 ETCO2 3 02 C0 FIG 48 U S Patent Apr 11 1995 Sheet 10 of 11 5 404 885 Sheet 11 of 11 5 404 885 Apr 11 1995 U S Patent 09 109 6 oe ome Go NEES N a i PZZ ZL ILL IIRI 5 404 885 1 FILTER UNIT FOR END TIDAL CARBON MONOXIDE MONITOR CROSS REFERENCE TO RELATED APPLICATIONS This is a divisional of U S Pat application No 07 990 425 filed Dec 15 1992 now abandoned which is a continuation in part of U S Pat application 07 899 261 filed Jun 16 1992
2. a NOdWNd ae fe 1 10 TWONVOy a YOSNIS 1 88 1 3 44 9 ROI ol Vo OIA 06 45 0 401 3 404 885 Sheet 4 of 11 11 1995 Apr U S Patent Gl 111100 3 8 ANIT WIYIS 8 31891 INIM 203 1 1 O T M aia ol 4 3 gZ 131 09 SINIA3 5 3 3 Q3IJILON G3WIL he tt WWW ZA sogna 51 09 ABYA ONY 7319 H NIA AING 31NdN09 93S Sb 80 7 00609 ZHIY00 TIdW S 1Y LUYIS f i eee A 410 annd LNOJWIL NING 80 T3ONVO IYSYN 39 14 SA3 3 139 9 Luvs 3 40 OUVOSAIY 5 3 3 0 1 USHOVdSIO 39 3 3 1 101 0181151338 5 3 3 0314110 SIN3A3 SANJAJ 1 1 3 314110 31341108 1811 11 6 341 4 LNOIWIL ZH WV LIH 81 09 319 4340 JOGHOLVA 3 8 831 11 8311111 SSYd MOT 3 3 314110 SONS S3TdWVS 0 1S 1 40 LUWLS YTANNYD WSYN 309 Id eu NO 00 WOOY I8ASVIN QNMOUHIVE OF 9 9 8 AV1dSI0 09 3141 13538 NO Y3M0d 00 NOUV oll Sheet 5 of 11 5 404 885 Apr 11 1995 U S Patent 131100 SAIN ANNIN TEET 09 09 318340 LW VINIL
3. 25 12 The analog input field wiring connectors J4 have pins J4 1 and J4 2 connected to amplifier interface board pins J2 1 and J2 2 respectively pin J4 3 connected to pin PL4 1 on the Servomex 1505 board and pin 14 4 connected to pin PL4 2 on the Servomex model 1505 board Analog input pins J5 RS232 port pins J7 and RS485 program pins J9 are not used The pins at key board interface J6 are used to connect a flat ribbon cable to the back panel of the display 90 LCD display device model LG LCD The pins J8 for the RS232 port are connected on the back panel to a conventional nine pin D sub connector The display 90 interface pins J10 are connected as follows Pin J10 10 are the common front panel buttons pin J10 12 is for button 1 pin J10 14 is for button 2 pin J10 16 is for button 3 and pin J10 18 is for button 4 Regarding the Servomex model 1505 circuit board it is connected as follows For device Power pin PL1 1 is connected to TB1 1 12 v pin PL1 2 is not con nected pin PL1 3 is connected to TB1 2 ground pin PL1 4 is connected to TB1 3 5 v For device Thermistor Status pins PL2 are not connected For device Nitrous Oxide Compensation pins PL3 1 and PL3 2 are jumpered and no other pins are connected For device Signal Output pins PL4 1 is connected to Little Giant pin J4 3 and pin PL4 2 is connected to Little Giant board J4 4 For device Remote Calibration Adjustment there are no pin connections Re
4. YALU JOOHILVM 1353 Y3 MOd 3 3 O I 0L YIHOIVASIO YISWNVW INIA 3 NOI LVZEWILINI i SINIA3 3 1 3183191938 SLNIA3 0314110 a SIN3A3 5 1 3 3 SIN3A3 3 3 OJON QIWI 11 10 11110 g SINJAJ 209 313 10 loa on ae INS EI N 209 ONJ 18 5 3 1 200 ONY 209 399 1d 3 4 209 ONY 09 J0V 14 1141 09 JUNSV3N 2 viva arya 09 JYNSYIN Ot 1 Viv el 1vo LUYIS 203 4 39 LV LUYIS 09 dfll3s S 9 200 8 199 SY9 03 81199 09 4 115 LIMI 21 Tor 01 eee Ce 139NY9 JANS 709 a III 209 dNLIS 009 BYA 8Y 09 135 a ROVIY 26 w TASO ON 3 404 885 Sheet 6 of 11 11 1995 Apr U S Patent ALIYYd ON dOLS 1188 80096 ZEZSY OZ 9 J UJANA 3 1 W02 ZEZSY 3A139334 1 4 WNSWO3HO W 300 14 311 VIVO 88 gg YIISNVUL SIN3A3 313410 3 SINJA 1 1110 03 Y3AIYO INN ZH N ZHEN 09 31VY3d0 Yai WIY3S 2625Y Luvs 13938 NO WaMOd catty 900HOIVA SINJA 0 1 na WaHOIVASIO YIIVNYN INIA 7 3 OAMI 38315138 51 3 3 03 110 SINIA3 SINJA NOIV ZITVI LINI JNN WOI SNOILISNVYL 31819 10901084 JNIHWW 31VIS JLINId 0901084 8 1 89 WASYOIHO W300WX 3 1 3161 INN WOI 38
5. _ A zr 11445 YIMOd nouda if ONHOLINS 77 E SYAN INd 0 4 p P Sn 9v0 LIP GOSI XINOAYIS Y34408 3V0 a or C os TT d0 1 ol ep a SIN oe as CoN Not Tug been Ler OEM 9 13 Ted TAM ZAY a Ser ler 0431 45 yee 8 YING 3 04 Osu FRM aL ef el SYOLIINNOJ 2s 2 a o JLA Lf omn 01 Indu anani soTwy 90 UIMOA INYU oC OlA 22758 TT QUVOG ONV 8 08 SNLLNNON 09 im 39VL10A 01 1NJYYNI 3 404 885 Sheet 3 of 11 11 1995 Apr U S Patent 140d WOI 94 INIT 2629 7 SAI ANIA 7 1 INT 09 1Y 31Y43d0 139NV9 1V UH WIYIS 262SY 1 YINI LUIS S00HOLVA USAIN CUVOGA IY 1153 NO YIMOd SINIA3 0 1 en AE USHOLVASI U3OVHVH eae SANJAJ 181 0343151994 5 3 3 03 110 oo 0 SLNIAI 1110 SINJA3 314110 SLNIAI SIN3AJ 314110 OJAIL YOUN VIVO 80 39 NONYT INIM SANJAJ 3141 10 983 Y0 WNSNIIHI ISN J9Nyy9 8NVIZANIN WAL LINSNVYL 100 ONY NIO EZI JUNSW3N 199 3 oll 190 NV SV 1910 1114 HOSN3S 221 3SNVd NOILISNYYL 209 03 121 QNNOUDNS E 7101 UWS 1000108 WIGONX ogi NOLLVOINANWOD VIVO MVI NNIW INN 98 AAYA
6. now U S Pat No 5 293 875 FIELD OF THE INVENTION This invention relates to methods and apparatus for invivo real time measurement of end tidal carbon mon oxide concentration in the exhaled breath more partic ularly to a filter unit for use in the determination of end tidal carbon monoxide concentration in the breath of a newborn infant BACKGROUND OF THE INVENTION In most animal systems carbon monoxide is a waste product produced in the breakdown of free hemoglobin within the blood Ordinarily hemoglobin is contained within red blood cells and is stable However aging of red blood cells and certain disease processes produce hemolysis i e the breakdown of the cell wall This produces free hemoglobin which breaks down in the blood The carbon monoxide that is produced by the breakdown of free hemoglobin is normally excreted in the breath When the system is in equilibrium the carbon monox ide concentration in the breath is proportional to the difference in the concentration of carbon monoxide in the blood and the concentration of carbon monoxide in room air This difference in concentration is propor tional to the rate of hemolysis in the blood The concentration of carbon monoxide in the end tidal breath i e the gas that is last expelled each breath is presumed to be at equilibrium with the concentration in the blood This is because the end tidal breath con tains predominantly if not exclusively the gas expelle
7. used for each of CO and CO2 From these two samples the foregoing gas calibration equations 2 and 3 for converting a provided voltage to a gas concentration are determined The calibration equations are reason ably accurate over the concentration ranges of interest e g accurate within 10 In one embodiment in sequences 131 and 133 a key board associated with display 90 may be used to input the test gas type and concentration data directly by pressing alphanumeric characters In accordance with a preferred embodiment using the Little Giant LCD dis play device select button 3 is used to toggle a digit that is underscored on the display screen menu between values to display the known gas concentration value The menu button 4 is used to move the underscore along the displayed characters for selecting the charac ter to be changed Start button 1 is used to indicate that the character now displayed is the correct value which value is then stored for use in deriving the cali bration function for the gas detector being calibrated The calibration is thus conducted in a known manner and preferably produces a linearized calibration func tion Preferably two samples of each gas at known concen trations are used Thus two points are obtained v1 p1 and v2 p2 where v1 and v2 are the measured voltages and pi and p2 are the corresponding known gas concen trations Using these two test points the calibration constants are co
8. 0 2 4 m 1 2 5 where Veo 1 corresponds to the signal produced by CO detector 70 at time t When pump 60 is stopped at time t at the conclusion of the background step 121 the CO is measured and the routine enters pause step 122 During the pause step 122 the operator is prompted to place the nasal cannula 10 inside the patient s nostril and then to press button 1 to resume the measurement sequence The system prefera bly displays a suitable message on display 90 e g place nasal cannula to prompt the user to place the cannula 10 The pause step 122 preferably includes a minimum delay period Timeout of about ten seconds and a maximum delay period Timeout of about five minutes Thus if the operator does not press the start button 1 within the Timeout period the system will return to the idle state 110 The Timeout period is used to provide for sampling the room air and patient carbon monoxide concentrations within a time period wherein it is not likely that the room air concentration level will change very much The Timeout period also is selected to permit the operator sufficient time to insert the nasal cannula 10 in a patient such as a newborn infant which may require some time to accomplish Once the cannula 10 is place the operator presses button 1 to resume the measurement sequence 123 At time t2 pump 60 is turned on for a second time period which is preferably the same as the fi
9. 0 3 cm This provides for full access to the entire cross sectional area of filter 45 by the analyte flow stream Tube segment 508 is preferably a length of vinyl tube having longitudinally extending ribs along the inner surface not shown The ribs prevent tube 508 from pinching off after it is bent and secured in place in unit 500 In this regard the ends of tube segment 508 are dipped in solvent and then inserted into lumen 506 and the inner passageway 511 of plug 510 to a depth suffi cient to retain tube 508 securely A suitable depth is about 1 0 cm Accordingly tube 508 may have an over all length of about 6 cm an outer diameter of about 0 3 cm and an inner diameter of about 0 15 cm Aker nately tube 508 may be frictionally fit into lumen 506 and passageway 511 In a preferred embodiment lumen 502 has an inner diameter of about 0 15 cm lumen 504 has an inner diameter of about 0 83 cm and lumen 506 has an inner diameter of about 0 3 cm connector 16a has a maxi mum outer diameter di of about 0 19 cm connector 166 has a maximum outer diameter d2 of about 0 87 cm and connector 16c has a maximum outer diameter d3 of about 0 34 cm The thickness of each lumen wall may be on the order of 0 15 cm such that there is about a 20 25 14 double thickness between adjacent lumens in the mid plane of unit 500 as illustrated in FIG 7 By using these dimensions which are exemplary and not critical the different lumen di
10. beeper for key pad feedback It is compatible with and directly inter faces with the Little Giant LG X miniature microcon troller Referring to FIG 2 a printed circuit board layout of 45 the Z World Little Giant microcontroller circuit board is illustrated and the interconnection of elements is de scribed using the manufacture s conventional pin con nections unless otherwise stated Referring to terminal board TB1 one or more AC DC regulated power 59 supplies not shown are used to provide the following signals to the four numbered input pins of terminal TB1 12 volts to pin 1 ground potential to pin 2 5 volts to pin 3 and 12 volts to pin 4 The corresponding four output pins of terminal board designated TB1 X 55 wherein X refers to the output pin are respectively connected in series with the input pins of TB1 and the pins of the apparatus illustrated in FIG 1 as follows Regarding microcontroller 80 the high current out put wiring connectors J1 have pin J1 8 connected to the 60 negative terminal of pump 60 for providing a current to drive pump 60 at the selected rate There are no other connections for wiring connectors J1 The power wir ing connectors J2 have pin J2 1 connected to J2 4 pin J2 2 connected to J2 3 pin J2 6 connected to TB1 2 65 ground pin J2 7 connected to TB1 4 12 v and no other J2 pin being connected The RS485 field wiring connectors J3 are not used in this embodiment
11. conditions over time Impor tantly with respect to newborn and premature new borns it provides for enhanced detection of potential problems before the newborns are discharged from the hospital One skilled in the art will appreciate that the present invention can be practiced by other than the described embodiments which are presented for purposes of illus tration and not of limitation We claim 1 A method of filtering a gas sample for use with a non invasive end tidal gas flow monitor containing a first sensor for detecting the amount of a first gas com ponent in a gas sample a second sensor for detecting the amount of a second gas component in the gas sample a first connector in communication with the first sensor a second connector in communication with the first sen sor a third connector in communication with the sec ond sensor comprising 50 55 60 65 22 providing a body having a first end and a second end and first second and third lumens extending through the body between the first and second ends providing a first consumable filtration medium for removing selected undesired components from the gas sample locating the first consumable filtration medium in one of the second and third lumens connecting the second and third lumens with a tube segment at one of the first and second ends thereby providing the first lumen as a first gas flow path between the first and second ends of the body and pr
12. detector has a time response to the analyte flow that produces an average carbon monoxide concentration The digitized samples corresponding to the carbon monoxide concentration are then processed so that the output signal is the aver age of the last five acquired samples Preferably the determined concentration value is displayed e g in parts per million ppm The amplitude of the voltage signal corresponding to the averaged sensed carbon monoxide concentration CO oom from detector 70 that is displayed also may be displayed for diagnostic pur poses The CO and CO gas equations used to convert the sampled voltage signals corresponding to the detector signal outputs to gas concentrations are CO ppm m veo c 2 CO2 m2 Veo2 2 3 where m and are the slope and intercept calibration constants relating the voltage Veo derived from the CO detector 70 output in response to the concentration of carbon monoxide in a sample to ppm and and c2 are the slope and intercept calibration constants relating the voltage Vco2 derived from the CO detector 30 output in response to the carbon dioxide concentration in a sam ple in percent Thus at time to with CO 0 ppm using the above equation O m Yeot c1 and 2 1 c1 mM Yco0 2 2 5 404 885 17 where Vco 0 corresponds to the signal produced by CO detector 70 at time to At time 1 COrcom ppm m 1 2 3 m YCO 1 VCO
13. embodiment the assembly is formed of a body having three flow paths also called lumens extending from one end to the other and a tube segment that is used to connect two of the flow paths at one end of the body The consumable filtration medium is 1o cated in one of the two lumens connected by the tube segment Thus the tube segment provides for a gas flow path from the carbon dioxide detector through the consumable filtration medium and to the carbon mon oxide detector Preferably the three lumens are straight and have longitudinal axes that are in the same plane More preferably the three lumens have different inte rior dimensions and respectively mate to corresponding differently sized bulkhead fittings on the monitor This ensures that the filter unit will be installed in the correct orientation with tight interconnections In the preferred embodiment the body and its lumens are formed by coextrusion of a single piece of plastic material e g soft polyvinyl chloride The consumable filtration medium is then inserted in one of the lumens of the second flow path A plug is inserted into the distal end of that lumen which has a flow passageway extend ing through the plug for receiving a length of the tube segment The piece of tubing is bent into a U shape to intercon nect the two selected lumens In this regard the tube segment preferably has an outer diameter that provides an air tight frictional fit when it is inserted in th
14. memory device or medium for subsequent analysis as desired The routine then exits the measuring sequence 120 and returns to the idle state at 110 The display preferably include the determined COzEr g in ppm and also may provide the duty cycle of the carbon dioxide waveform corresponding to the end tidal portion and or various voltages from the detectors 30 and 70 such as minimum and maximum voltages corresponding to CO and CO and initial and final voltages for COmean and or CO during the second time period It is noted that in connection with the second time period for monitoring the patient s breath ing the time references and t may be used in place of time references 2 and t3 respectively Preferably the data from the measurement cycle just finished will remain displayed for a period of time to allow the operator to record manually the data The display 90 may be cleared by pressing button 1 or reset 2 Following measurement of a sample the aforementioned delay time period of about one minute or three minutes is provided to allow the CO and CO2 detectors 70 and 30 to decay to a zero state before the next background measurement cycle begins Preferably any attempt to obtain another measurement before the end of the delay period will be simply delayed until the 10 15 20 25 30 35 40 45 30 35 60 65 20 expiration of that time and then automatically com mence Referri
15. the carbon dioxide concentration are evaluated to determine the duty cycle correspond ing to the end tidal portion of the patient s breath An average of the end tidal CO2 concentration CO2z7 to the average CO is obtained providing the duty cycle de The end tidal CO concentration COg7 is then determined from the following relationship COET COmean COroom de 1 where COmeanis the average or mean carbon monoxide concentration at the end of the second period and dc is the duty cycle determined for CO2 7 Referring to FIG 1 the macro flow diagrams of FIGS 2A to 2D a preferred embodiment of the opera tion of the present invention is now described In this embodiment display device 90 is configured to use four buttons which are used for controlling the operation of the apparatus Button 1 is a start button to initiate some action by the apparatus to reset the apparatus operation button 2 is a reset button button 3 is a select button to select some option from a menu and button 4 is a menu button to display one or more instruction and or operation menu Each button is acti vated by pressing in and then releasing the button Other alternatives for providing user input in an interac tive device may of course be used Referring to FIG 2A the device becomes activated on power on or reset pressing button 2 and enters an initialization sequence at step 100 During initialization the operating code of
16. to provide improved non invasive apparatus and methods for measuring carbon monoxide concentration in the end tidal breath It is another object to provide appara tus and methods that operate in real time It is another object to provide apparatus and methods for use in determining the rate of hemolysis from the concentra tion of end tidal carbon monoxide It is another object of the present invention to pro vide apparatus and methods for measuring end tidal carbon monoxide that do not require a highly skilled trained individual to obtain and determine the measure It is another object to provide such apparatus and meth ods that do not require incrementally acquiring samples of end tidal breath during successive respiratory cycles It is another object of the invention to provide a portable easy to use apparatus that can be used in a nursery a physician s office a hospital a clinic and a mobile clinic for measuring end tidal carbon monoxide in real time for assessing the likelihood of elevated levels of hemolysis for immediate entry on the patient s record and prescription of an appropriate remedy It is another object of this invention to provide an end tidal carbon monoxide monitor with a replaceable filter unit for use with different patients and for replac ing consumed gas filtering components It is another object to provide an inexpensive disposable filter unit It is another object of this invention to provide keyed bul
17. tubing 14b and the input port 20 of a carbon dioxide detector 30 Detector 30 has a gas sample cell and is used to provide a signal corresponding to the sensed concentration of carbon dioxide in the gas The detector 30 has a re sponse time that is sufficiently fast to distinguish the concentration level of the end tidal portion from the other portions of the breath Thus the signal changes in response to changes in the concentration of carbon dioxide in the breath as the patient breathes The resul tant signal waveform is used as described below to determine the ratio of the end tidal portion of the breath to the entire inspired air This ratio referred to as the duty cycle de is used to convert the detected carbon monoxide concentration CO to the end tidal car bon monoxide concentration COgr as described below One suitable carbon dioxide gas analyzer is the com mercially available Servomex model 1505 fast response carbon dioxide infrared transducer which is available from Servomex Company 90 Kerry Place Norwood Mass 02062 This device is a temperature compensated sealed transducer that is based upon a single beam sin gle wavelength technique absorption for measuring carbon dioxide It has a complete optical bench and uses a fast infra red carrier which is attenuated by the infra red absorption of carbon dioxide in the gas The device has detection circuitry that will convert fast changes of attenuatio
18. 1 is preferably open Canula 10 also has a tapered receptacle 610 which is configured to mate securely with a tapered protrusion 15 See FIG 6 of filter 15 in a conventional manner 35 40 45 50 55 60 65 Insertion mark 601 provides a depth gauge for the user to insert end 11 into the patient s nostril e g until insertion mark 601 enters the nostril Apertures 602 and 603 are spaced equidistantly between mark 601 and end 11 and located on opposite sides of the tubing Aper tures 602 and 603 extend only through one side of tube 10 More or different apertures and different aperture locations also may be used One suitable tube is model No 1219 15 5FRx36 feeding tube available from Medovations Inc Milwaukee Wis USA which is customized as noted and which mates directly to the tapered protrusion of filter 15 Preferably canula 10 is separately packed in a sterile package which is opened immediately prior to use In this regard filter 15 and fitting 605 may be provided together with canula 10 in sterile packaging separate from canula 10 and filter unit 500 in clean packaging or together with filter unit 500 and optionally completely or partially preassembled therewith in clean packag ing If desired the complete canula 10 filter 15 and filter unit 500 could be preassembled and packed in sterile packaging According to a preferred embodiment of the present invention the end tidal carbon monoxide
19. G 6 is an exploded isometric view of the filter of FIG 5 FIG 7 is a top cross sectional view taken along line 7 7 of FIG 5 FIG 8 is an end view taken along line 8 8 of FIG 5 and FIG 9 is a top view of an alternate embodiment of a nasal canula of FIG 1 DETAILED DESCRIPTION OF THE INVENTION Referring to FIG 1 a preferred embodiment of the present invention relates to methods and apparatus for monitoring breath flow of a patient over a period of time and determining the end tidal concentration of carbon monoxide in the breath The apparatus includes a nasal cannula 10 a carbon dioxide detector 30 an organic vapor filter 45 a flow regulator 50 a pump 60 a carbon monoxide detector 70 and a microcontroller 80 Preferably a hydrophobic filter 15 is provided be tween the cannula 10 and the gas detectors to remove moisture from the sample of breath In particular filter 15 is used so that moisture does not interfere with de tecting carbon dioxide Filter 15 is illustrated in FIG 1 as inserted between tube 14a which includes cannula 10 and a connector 16a which is secured to the base 5 which supports and preferably encloses the gas detec tors 30 and 70 pump 60 and flow regulator 50 One suitable hydrophobic filter 15 is part number 51190 available from Filtertek Inc Cannula 10 is one segment of tubing 14a which has one end 11 that is adapted for insertion into the nostril posterior nasal pharynx of a normall
20. This may be calculated in a straightforward manner from the acquired data The foregoing equations are based on the realization that the physical behavior of CO and CO are very similar with respect to for example diffusion flow rates and other behavior characteristics in the patient s cardiopulmonary system Accordingly it can be as sumed that ratio of the end tidal CO2 to the total CO 15 the same as the ratio of the end tidal CO to the total CO This is illustrated in FIGS 4a and 4B Further it can be assumed that the CO2 concentration of room air is ap proximately 0 and that the end tidal CO2 concentration is related to the duty cycle of the breath waveform and the mean value of the CO concentration namely CO2ET dc CO2mean 5 Thus based on these assumptions the CO and CO ratios are CO2ET CO2z00m a CO2mean de 0 CO2mean CO2r00m COET COrom COmean COroom and thus COet COroom 1 de O mean and the total end tidal COgris COmean COroom 0 COroom dc Therefore to obtain the patient s actual end tidal CO level produced the portion of the patient s breath from the COroom concentration i e the CO level that was inhaled by the patient must be subtracted from the total which yields the equation 1 above The determined values are then displayed on display 90 and any desired printouts of the acquired data may be made or stored to a
21. United States Patent Sheehan et al US005404885A 1 Patent Number 45 Date of Patent 5 404 885 Apr 11 1995 54 FILTER UNIT FOR END TIDAL CARBON MONOXIDE MONITOR 75 Inventors Neil J Sheehan Palo Alto Scott R Rouw Union City Robert T Stone Sunnyvale all of Calif 73 Assignee Natus Medical Incorporated San Carlos Calif 21 Appl No 184 379 22 Filed Jan 21 1994 Related U S Application Data 60 Division of Ser No 990 425 Dec 15 1992 aban doned which is a continuation in part of Ser No 899 261 Jun 16 1992 Pat No 5 293 875 618 5 08 52 5 128 716 128 719 128 204 22 422 83 73 23 3 58 Field of 128 716 719 204 22 128 204 23 205 22 422 83 84 73 23 3 56 References Cited U S PATENT DOCUMENTS 3 977 394 8 1976 Jones et al 128 2 07 4 304 578 12 1981 Hakala et al 128 719 4 423 739 1 1984 Passaro et al 128 719 4 821 737 4 1989 Nelson 128 719 4 831 024 5 1989 Vreman et al 514 185 4 870 961 10 1989 Barnard 128 205 12 4 886 528 11 1989 Aaltonen et al 128 719 4 968 887 11 1990 Wong 250 343 5 003 985 4 1991 White 364 413 03 OTHER PUBLICATIONS Yeung et al Automatic End Expiratory Air Sampling Device For Breath H
22. ain filter 45 as the assembly is inserted into lumen 504 and provide a flow path through filter 45 with an ac ceptable pressure drop In this regard cap 512 is seal ingly interposed between filter and lumen 504 so that the analyte flow stream through lumen 504 will pass through filter 45 and inside cap 512 and not around filter 45 or cap 512 Filter 45 is preferably assembled as a sandwich of acetate 46b carbon 45a and acetate 460 such that at least one acetate section 46b and carbon 46a is inserted into cap 512 The assembled cap 512 and filter 45 is then press fit inserted into lumen 504 to an appropriate depth Preferably filter 45 is finally located to be cen tered about the midpoint of lumen 504 It is important that an organic lubricant not be used to insert cap 512 into lumen 504 Water may be used as a lubricant if necessary Plug 510 is a cylindrical plug made of PVC that is inserted into lumen 504 on the end 503 side of filter 45 Plug 510 has a length d21 of about 1 0 cm and an air flow passageway 511 extending through its longitudinal axis having an inner diameter of about 0 3 cm The length is not critical but must be sufficient to retain tube segment 508 Plug 510 may be secured into lumen 50 by dipping it in a solvent and inserting the dipped part into lumen 504 from end 503 so that they bond together In a preferred embodiment when fully seated cap 512 is spaced from the inner end of plug 510 by a distance d11 of about
23. ameters may be frictionally fit se curely only onto the correspondingly sized bulkhead connectors 16a 16b and 16c see FIG 7 This assures that filter unit 500 will be correctly connected to moni tor 5 Alternate spacing or orientation of the three lu mens and the corresponding bulkhead connectors could be used to accomplish the same function Also the bulkhead connectors could be recessed so that filter 500 is supported by both the recess and the connectors Referring to FIGS 6 and 9 a preferred embodiment of the invention employs obtaining a gas sample using canula 10 a fitting 605 and hydrophobic filter 15 Fit ting 605 is preferably a male tapered luer with an inte gral locking ring and a barb 606 for a 1 16 0 159 cm inner diameter tube It is designed to pass into lumen 502 of filter unit 500 and remain securely connected by a frictional fit Fitting 605 may be made of nylon prefer ably a white nylon One such suitable fitting is part no MTLL210 1 available from Value Plastics Inc Fort Collins Colo USA Filter 15 may be a part No 3 0 mm filter F1 57120 available from Filtertek Hebron Ill USA which screws directly into the patient side of fitting 605 Canula 10 is preferably a length of plastic tube such as an infant feeding tube with a distal tip that has been modified to provide an insertion mark 601 and two apertures 602 and 603 all located within a distance d31 of about one centimeter of end 11 End 1
24. art One advantage of the present invention that it pro vides a simple and easy to use device that accurately and relatively quickly obtains a measure of the end tidal carbon monoxide concentration of a patient The deter mination is made immediately following acquisition of the breath sample and is thus performed in real time It overcomes the above noted problems of the prior art techniques Another advantage of the invention is that it provides a reusable apparatus with a disposable canula and a disposable filter unit containing a consumable organic filtration medium This facilitates quick and easy replacement of parts requiring replacement due to the end of their useful life while maintaining the durable measuring apparatus intact The disposable filter unit is particularly advantageous because it incorporates con ventional materials processing which can be performed in high volume production runs at low cost and uses simple inexpensive assembly procedures rather than more complicated fabrication techniques to obtain very low cost units Similarly the use of off the shelf fittings and hydrophobic filters provides additional cost savings over proprietary products The present invention is particularly useful for detecting abnormal levels of he molysis in newborn and premature infants as well as determining incipient hyperbilirubinemia elevated lev els of bilirubin the likelihood of the onset of jaundice and the resolution of those
25. ath can be used to determine the carbon monoxide and carbon dioxide concentrations without affecting the sample particularly when the sample stream is passed through an infrared absorption type carbon dioxide detector prior to an electrochemical cell type carbon monoxide detector In addition the use of an exhaled gas carbon dioxide or another provides a non intrusive and non invasive technique for determining the duty cycle dc It does not require an additional or alternate sensor or transducer on or near the patient and it does not require additional patient cooperation or discom fort Furthermore using one time sample of breath to determine the duty cycle of end tidal breath is more accurate than visually monitoring chest wall movement or respiratory activity over a period of breathing cycles or relying on a predetermined breathing rate which are subject to change and attempting to obtain samples of exhaled breath only during end tidal portions Other gas sensors may be used e g oxygen which would have a relatively reduced concentration level during end tidal breath or hydrogen which would have a relatively increased concentration level during end tidal breath Two different gas detectors e g car bon dioxide and hydrogen could be used to identify the end tidal portion wherein carbon dioxide provides a fast response and hydrogen provides a slow response to changes in concentration Another advantage of the invention with respe
26. concentration the patient is measured in the following manner An initial value of carbon monoxide may be obtained for analysis purposes Pump 60 is then started and a sample of room air is drawn through monitor 5 at the selected flow rate of e g 50 ml min past the carbon dioxide detector 30 and the carbon monoxide detector 70 At the end of a first time period e g 45 seconds the mea sures of the concentrations of the carbon dioxide and carbon monoxide in the sample cells of the carbon diox ide sensor 30 and carbon monoxide sensor 70 are ob 5 404 885 15 tained respectively The measures are obtained as ana log signals from the detectors 70 and 30 e g sensed currents converted to conditioned voltages Ve and which are respectively digitized into n bit words n is preferably 8 at selected sampling rates and passed into a data buffer and or memory The values are stored as COroom and COzzero Pump 60 is then turned off and the cannula 10 is placed in the patient s nostril preferably in the posterior nasal pharynx Then the pump 60 is turned on again and an analyte stream of breath is drawn past the respective gas detectors 70 and 30 The concentrations of carbon monoxide and carbon dioxide are respectively sensed and sampled during a second time period e g 45 sec onds The acquired measures of the carbon dioxide concen tration over the second time period are evaluated First the relative changes in
27. ct to relying on changes in gas concentration levels is that the measurement decouples the breath gas concentrations from rhythmic respiratory activity In other words pump 60 may be used to provide a gas flow rate through cannula 10 and the flow path that is greater than the patient s respiratory flow This in turn provides an end tidal waveform stretching that enhances evalua tion of the gas concentrations and determination of the end tidal portion of the breath based on a breath gas It also provides for synchronization between the respira tory activity corresponding to the end tidal portion based on carbon dioxide and the detection of carbon monoxide concentration in the same breath sample flow Consequently the carbon monoxide concentra tion may be calculated based on post data acquisition processing analysis of the last acquired sample As a result the end tidal carbon monoxide determination is effectively provided in real time and without the delay occasioned by the previously reported techniques In addition the present invention avoids reliance on a previously established breathing cycle or rate to predict when chest wall movement coincides with end tidal flow Instead the invention is completely responsive to changes in the patient s breathing rate and volume as the sample is acquired The prior known techniques are not The gas flow output 40 of detector 30 is in turn con nected to a piece of tubing 14c and passed t
28. d from the alveoli in the lungs which gas was within the alveoli for a time generally sufficient to equilibrate with the blood It is known that hemolysis and the resulting by products and consequences of hemolysis can be esti mated or predicted from a measure of the concentration of carbon monoxide in the end tidal breath See Smith D W et al Neonatal Bilirubin Production Estimated from End Tidal Carbon Monoxide Concentration Journal of Pediatric Gastroenterology and Nutrition 3 77 80 1984 One method of analysis previously reported includes incrementally acquiring a sample of end tidal breath and analyzing the acquired sample by mass spectros copy or gas chromatography to determine the end tidal carbon monoxide concentration The sample is obtained by extracting from each of several successive breaths a portion of the apparent end tidal breath using a syringe The end tidal portion of breath is determined by observ ing the chest movements of the infant See e g Vreman et al U S Pat No 4 831 024 One problem with this technique is that it requires a skilled trained user to obtain the end tidal sample in successive increments based on watching chest wall movements It also requires a trained skilled person to operate a complex piece of analytical laboratory equip 5 10 15 20 25 30 35 45 50 55 65 2 ment to analyze the acquired sample In addition this technique requires time and per
29. e change in concentration with breath ing Other gases may be used e g hydrogen oxygen or some combination of gases e g carbon dioxide and hydrogen The determined end tidal carbon monoxide concen tration may be used by a physician or other suitable health care provider to evaluate the rate or relative level of hemolysis occurring in the infant The evalua tion is typically made by comparing the determined end tidal carbon monoxide concentration to known or preselected standards For example when measured soon after birth the end tidal carbon monoxide range 0 6 1 9 is considered normal and the range above about 2 ul l is considered at risk Premature infants have both a higher risk of neonatal jaundice and a higher normal range of end tidal carbon monoxide Another aspect of the present invention concerns a disposable filter unit that contains the consumable filtra tion medium One embodiment of this aspect of the invention provides an assembly to direct the gas flow through the monitor having two distinct flow paths One flow path provides for receiving the breath flow 5 5 20 25 35 40 45 50 55 60 65 4 sampled at the patient into the monitor more specifi cally from the nasal canula to the carbon dioxide detec tor The second flow path contains the consumable filtration medium and provides a flow path between the carbon dioxide sensor and the carbon monoxide sensor In a preferred
30. e plug flow passageway and the other lumen of the second flow path Preferably the tubing has interior ribs along its length to minimize the likelihood of the tube collaps ing or pinching closed when it inserted in the paths The tube segment is preferably secured to each of the plug flow passageway and the other lumen which are of about the same inner dimension diameter by a con ventional solvent dipping and bonding process Another aspect of the invention is directed to provid ing a hydrophobic filter that plugs into the distal end of the lumen of the filter unit forming the first flow path A conventional fitting for receiving the hydrophobic filter is interposed between the canula tubing that is used to take the breath sample from the patient and the filter unit This construction is particularly advanta geous because the filter and fitting elements are quickly and easily assembled by the end user and alternately can be provided in a preassembled configuration in a clean but not necessarily sterile package In addition it also is extremely low cost because it uses a combination of conventional commercial parts The present invention provides a tool for predicting the likelihood that the determined level of hemolysis will lead to adverse consequences such as jaundice and hyperbilirubinemia which might not appear for several days Thus the apparatus and methods of the present invention provide for reliable detection and early trea
31. ed at the sensing electrode which produces a current proportional to the carbon monoxide partial pressure The device is temperature compensated It has a concentration sensitivity in the range up to 500 ppm and provides an output current of 0 1340 4 pA ppm and requires about 20 seconds to equilibrate fully with the gas sample being monitored it has a reaction half life of ten seconds Microcontroller 80 is used to control the operation of the apparatus Microcontroller 80 receives signals re lated to the output signals from carbon dioxide detector 30 and carbon monoxide detector 70 corresponding to the sensed instantaneous carbon dioxide concentration and sensed average carbon monoxide concentration respectively These received signals are processed to compute a value corresponding to the end tidal carbon monoxide concentration in the patient s breath as de scribed below The computed value may then be dis played on a display 90 such as a liquid crystal display device Preferably a conventional digital microcontroller system is used having a suitable software controlled microprocessor memory analog to digital conversion and signal conditioning functions Of course as will be apparent to persons of ordinary skill in the art discrete analog circuit elements and solid state finite state ma chines also may be used to control the operation of the elements and obtain the concentration measurement One suitable digital microcontroll
32. er is the model Little Giant LG X miniature microcontroller available from Z World Engineering Davis Calif The mi crocontroller 80 is connected to carbon dioxide detec tor 30 carbon monoxide detector 70 pump 60 and flow regulator 50 if one is used to operate and or receive signals from those devices An amplifier interface cir cuit 82 is used to provide for current to voltage conver sion of the signals provided by carbon monoxide detec tor 70 Referring to FIG 2E interface circuit 82 includes three amplifiers U1B U2B and U3B which are prefera bly OP290 low noise dual operational amplifiers avail able from Precision Monolithics Inc Santa Clara Calif Amplifier U2B is configured as a current to volt age converter having a 0 1 uf capacitor C3 in parallel with a 5 resistor R1 in the feedback loop The gain is determined by resistor R1 Amplifier U1B is a second order lowpass filter with approximately a 0 5 second time constant using two 4 resistors R2 and R3 and two 1 pf capacitors C2 and C3 configured as shown The filter is used to attenu ate electrical noise Amplifier U3B is configured as a simple amplifier with gain adjustment potentiometer 100KQ in series with a 10kQ resistor R7 both of which are in parallel with a 0 1 uf capacitor C4 in the feedback loop and a 10k input resistor R4 at the inverting amplifier input Potentiometer R8 is used to allow initial calibra tion to compensate for
33. ference is made to the user manual for the device entitled Little Giant Single Board Computer Technical Manual Version E which is available from 15 the manufacturer for information regarding configur ing and implementing use of the microcontroller The display device 90 is capable of providing a dis play corresponding to the determined carbon monoxide concentration level in the end tidal breath COgr Pref erably display 90 includes a display screen for alphanu meric text including the determined concentra tion and preferably instructions to the operator for operating the device to acquire the appropriate gas samples Further display device 90 is preferably user interactive and includes both a keyboard for operator input and a visual display for prompting the operator to act Also the display device 90 may include a paper printer or have an associated printer not shown for 30 providing a printed copy of the parameters determined and or measured in character text or graphic form Alternately or in addition audible sounds visual indi cators or lights may be used to prompt the operator to perform the appropriate act 35 One suitable display device is a model LG LCD keypad liquid crystal display device available from Z World Engineering This device has definable function keys on a keyboard and a visual character display The visual display includes a 2 line by 16 character LCD 40 The keyboard has a 4X4 keypad and a
34. ferring now to FIGS 5 9 in a preferred embodi ment of the invention the segment of tubing between hydrophobic filter 15 and fitting 16a and the tubing segment between fittings 16b and 16 the segments illustrated as 14d in FIG 1 are formed as part of a disposable filter unit 500 Filter unit 500 is preferably constructed as a single housing having three lumens 502 504 and 506 and a tube segment 508 that is used to connect together lumens 504 and 506 as described in more detail below Filter unit 500 is preferably made of a soft polyvinyl chloride PVC more preferably a single extruded body having the three lumens that is made of soft PVC The outer surface of filter unit 500 may have a ribbed surface for example longitudinal ribs for a distinctive appearance horizontal ribs to im prove gripping or both Preferably the three lumens are extruded with their longitudinal axes lying in a com mon plane and with different inner diameters as illus trated in FIG 8 In alternate constructions filter unit 500 may be formed of three separate extrusions that are glued or otherwise secured together and the three lumens may be spaced with their respective axes offset vertically and or horizontally within filter unit 500 Filter unit 500 has a unit facing end 501 a distal end 503 a plug 510 a cap 512 and filter 45 Filter 45 is inserted into cap 512 and together they are passed into the interior of lumen 504 Filter 45 comprises a le
35. he Little Giant LG X mi crocontroller 80 is programmable using Z World s Dy namic C language It uses about 200 mA contains a microprocessor Z180 having a 9 216 MHz clock fre quency and sufficient memory including read only memory ROM random access memory RAM and erasable programmable read only memory EPROM which collectively contain the software data and mem ory address locations for operating the apparatus pro cessing the acquired data and performing the data ma nipulation and post acquisition processing functions in accordance with the present invention as described herein The device also contains counter timers includ ing a 2 Hz watchdog timer for automatically resetting the microprocessor in the event of undefined operations 5 404 885 11 or temporary power loss serial input output ports parallel input output ports time and date clocks multi channel analog to digital converter a digital to analog converter operational amplifiers for input signal condi tioning in single ended or double ended modes adjust 5 able gain and input voltage ranges a high current driver output suitable for driving pump 60 and other particu lar elements provided by the manufacturer which either are used in a conventional manner although not perti nent to the present invention or are not used The mi 10 crocontroller is used in accordance with the manufac turer s directions and specifications except as otherwise noted and re
36. he desired gas flow rate in the range of 40 60 ml min One suitable pump is model NMP 02 diaphragm micro pump available from KNF Neu berger Inc Princeton N J which has a free flow ca pacity of 0 22 to 0 55 L min Pump 60 and flow regula tor 50 may be located anywhere in the flow stream preferably between the carbon dioxide detector 30 and carbon monoxide detector 70 inside the enclosure of base 5 Pump 60 also passes the analyte flow stream out exhaust 75 downstream of the gas detectors 30 and 70 of the apparatus Carbon monoxide detector 70 is preferably an elec trochemical sensor that produces an electrical current proportional to the concentration of reducing gases such as carbon monoxide which are present in the gas at the gas permeable membrane of detector 70 not shown The response time of the carbon monoxide detector 70 and the averaging function of the filter 45 preferably result in a signal output from the detector 70 that is proportional to the average concentration of the reducing gas at the membrane 5 404 885 9 One suitable carbon monoxide sensor is model Drag erSensor CO available from Dragerwerke of Lubeck Germany It has a plastic gas permeable membrane a liquid electrolyte sensing reference and counter elec trodes in the electrolyte and a potentiostatic circuit that maintains a constant voltage between the sensing and reference electrodes The carbon monoxide in the gas is electrochemically convert
37. hrough connector 16b into tube segment 144 Tube segment 14d contains an organic vapor filter 45 Filter 45 may con tain any medium that will absorb organic vapors and reducing gases that might interfere with detecting car bon monoxide levels in the carbon monoxide detector 10 Filter 45 preferably contains activated charcoal It is preferably constructed as a canister that either can be 5 20 25 30 40 45 55 60 65 8 inserted interior to the flow path of tube 14d or is in serted between two segments of tubing such that the analyte gas stream passes through the canister Filter 45 illustrated in FIG 1 connected between two connectors 16b and 16c so that it is external to base 5 This provides for simple and quick replacement of filter 45 when it is substantially consumed Filter 45 may be an inexpensive disposable portion of the apparatus One advantage to using filter 45 is that it tends to average the concentrations of gas in the analyte stream by thoroughly mixing the stream within the volume of filter 45 A preferred construction of filter 45 is to use a 20 mm length of charcoal rod having a circumference of 24 4 mm which is sandwiched between 3 0 mm seg ments of white acetate having the same circumference The charcoal rod is preferably cut from Filtrona AAD Charcoal Filter Rods available from American Filtrona Corp Richmond Va Where desired more than one carbon rod segment may be used provided that pum
38. icular conditions of use Following acquisition of the data the data is pro cessed by the microprocessor Z180 of microcontroller 80 to derive the duty cycle and the end tidal CO con centration COzr The digitized samples of the voltage Vco are passed through a low pass digital filter which may be implemented by suitable software which takes an average of the last five samples This filter is used to suppress noise It also advantageously permits use of the output of the digital filter without further averaging or storage of separate values The corresponding average or mean CO concentration at time t3 COmean is thus COmean m Vm c1 4 where Vm 15 the average of the last five voltage samples Vecos The duty cycle dc is calculated based on analysis of the sampled voltages 2 between time t and t3 as follows the number of CO2 samples gt VA ftotal number of CO samples the number of CO2 samples gt 1 5 total number of CO samples de where V 15 a selected threshold voltage corresponding to e g a 1 5 CO2 concentration and is obtained from the CO2 gas equation 3 as follows 15 mz2 Vi 0 Vr 1 5 c2 m2 For an ideal CO2 detector 70 m2 10 and c2 0 such that V 0 15 volts Of course other values and thresh old voltages could be used as appropriate in the particu lar circumstances Then the patient s end tidal CO concentration COgr is COrT COmean COreom de 0 5 404 885 19
39. khead fittings on the monitor for receiving the filter in the correct orientation and to provide for proper flow path interconnection and operation of the dispos able filter in the monitor In accordance with this invention there is provided an apparatus sampling methods and analysis tech niques for measuring the concentration of end tidal carbon monoxide in breath particularly in newborn and premature infants Broadly the invention concerns de 5 404 885 3 termining the concentration of end tidal carbon monox ide based on a measure of the room air carbon monoxide concentration a measure of the average carbon monox ide concentration for a breath sample over a period of time and a determined ratio of the end tidal breath to inspired air for the sampled portion The present invention is based in part on the discov ery that accurate assessment of end tidal carbon monox ide concentration may be obtained based on knowledge of the fraction of the gas sample that is end tidal gas Thus the present invention is able to avoid selectively sampling small samples of end tidal breath over succes sive respiratory cycles to obtain a sufficiently large end tidal breath sample which incremental sampling is problematic Further the invention advantageously uses a conventional carbon monoxide detector which has a response time that is not fast enough to distinguish carbon monoxide in end tidal breath from carbon mon oxide in inspired air
40. laim 7 wherein providing the body further comprises forming the body as an extruded or molded tri lumen tube 9 The method of claim 7 wherein inserting the tube segment further comprises bonding the tube segment to the plug flow passageway and the other of the second and third lumens 10 The method of claim 5 further comprising provid ing the lumens with longitudinal axes in a common plane 11 The method of claim 5 further comprising form ing the first second and third lumens with dimensions for interconnecting to the first second and third con nectors to form a secure frictional engagement 12 The method of claim 1 wherein providing the first filtration medium further comprises providing a first length of cellulose acetate providing a second length of cellulose acetate providing a length of activated carbon having an outer circumference and positioning the length of activated carbon between the first and second lengths of cellulose acetate 13 The method of claim 12 further comprising seal ingly interposing a thin cap between the outer circum ference of the activated carbon and an interior wall of 5 404 885 23 the second gas flow path and providing the cap with an aperture at each end of the carbon for providing a gas flow path therethrough 14 The method of claim 1 further comprising providing a fitting having a barbed end for connect ing to one end of the first lumen providing a hydrophobic filter a
41. ler based device containing a carbon dioxide detector a carbon monoxide detect and a pump for use in a hospital home physician s office or clinic by persons not requiring high skill and training is described A replaceable filter unit made of a single tri lumen PVC extrusion and a tube segment inter connecting two of the lumens used to provide the consumable filtration material The filtra tion material is interposed between the carbon dioxide sensor and the carbon monoxide sensor which are mounted inside the monitor housing The filter unit also interfaces the canula for receiving the patient s breath sample and a hydrophobic filter between the patient and the carbon dioxide monitor 16 Claims 11 Drawing Sheets 5 404 885 Sheet 1 of 11 11 1995 Apr U S Patent 28 Eog 8 EENE Lo Ny 06 A anli NI 0 Y ie E 02 18 1 9 149 S Q 40193130 348 ae E a lt 209 Pol 091 Ob F VIIA e Y E e nea JINYIYO a 7 213 40193130 0L 23 a Sheet 2 of 11 5 404 885 Apr 11 1995 U S Patent TWOULUSA IVIIIYJA TWNOZTYOH OYYO8 YOSSIOUAOYIIN ISOdYNd LINW qwouyan 9 8304 1831 198 INVIO 11111 080 7 yowr Y3MOd CESA iC Re ee ee nouns n O DJ op Ceia mAT E F10H INILNNOW l eh 0812 HONE
42. microcontroller 80 is booted and various system checks and device initializations are performed Following initialization the routine passes to an idle state at step 110 where it waits for user input During the idle state the system preferably generates a suitable message on display 90 e g Ready press 1 to start Thus during the idle step 110 the user may provide an input by pressing button 1 to start a mea suring sequence This passes the operating routine to step 120 Also during the idle state 110 the operator may press button 3 to select a sequence from a menu displayed on the display unit 90 and button 4 to display various operation sequences One such sequence is a calibration routine for calibrating the carbon monoxide detector 70 and carbon dioxide detector 30 at step 130 The opera tor also may press button 2 at any time to exit what ever routine it is executing reset the apparatus and return the routine to step 100 Referring to FIGS 2A and 2B in response to press ing button 1 in the idle state 110 the routine moves 15 20 25 30 35 45 50 55 60 65 16 from the idle step 110 to step 120 for the sequence for determining end tidal carbon monoxide concentration COer There are three phases to this determination a sequence at step 121 for measuring the background carbon monoxide CO oom during a first time period a pause or delay period at step 122 and a sequence at step 123 fo
43. n into an electrical output signal The Servomex model 1505 transducer is used in ac cordance with the manufacturers directions and specifi cations It provides under constant conditions a linear output voltage of from 0 to 1 0 volts corresponding to from 0 to 10 carbon dioxide and is extendable up to 1 5 volts corresponding to 15 carbon dioxide The response time is on the order of 120 ms at a flow of 100 ml min and the flow rates may be in the range of from 50 200 ml min Other carbon dioxide measuring de vices also could be used It should be understood that any device that is capa ble of determining the duty cycle of end tidal breath to inspired air over a given period of time may be used in place of the carbon dioxide detector provided that the determined duty cycle is for the same period of time during which the sample on which the carbon monox ide concentration determination is based was acquired Such a device may be a spirometer for measuring flow velocity or flow volume a non breath flow device for monitoring breathing e g an impedance pneumo graph a microphone sensor and the like Also a breath gas detector for monitoring a breath gas other than carbon dioxide may be used 5 404 885 7 The carbon dioxide detector is preferred because changes in CO2 concentrations related to end tidal flow are relatively large and easily detectable using a thresh old level of carbon dioxide Further the same sample of bre
44. nd connecting the hydrophobic filter to the fitting 15 The method of claim 14 further comprising pro viding a canula having a first end and a second end the first end having a first and second aperture for receiving 10 15 20 25 30 35 45 50 35 65 24 said sample of gas from the patient and marking the canula with an insertion mark at a distance from the first end on the order of 1 0 centimeter and connecting the second end to the hydrophobic filter 16 The apparatus of claim 14 wherein the passing step further comprises passing said gas sample in se quence through said hydrophobic filter said first sen sor said first consumable filtration medium and said second sensor
45. ng to FIGS 2A and 2C the CO and CO detectors 70 and 30 are periodically calibrated using conventional CO and CO3 gases having known concen trations To begin the calibration sequence 130 the system must be in the idle state 110 The operator then presses button 4 to call the menu up on display 90 The menu will display an appropriate message such as menu 1 Calibrate CO CO2 sensor Activate button 1 to start The operator then presses button 1 which begins the calibration sequence 130 The calibration sequence involves the selection of test gases of known concentrations inputting the known concentration val ues into the system during set up sequence 131 for CO and setup sequence 133 for CO2 operating the pump 60 to draw the known gas into the system and determining the signal level produced by the detector 30 or 70 depending on the gas only one detector is calibrated at a time in response to the known gas concentration during measurement sequence 132 for CO and measure ment sequence 134 for CO2 In a preferred embodiment the display 90 is used to provide a sequence of instructions for the operator to input data such as which gas detector is to be calibrated and the concentration of the test gas that is to be used sequences 131 and 133 This is followed by providing a sample of that test gas which is then sampled and measured sequences 132 and 134 Preferably at least two gas samples at different known concentrations are
46. ngth of activated carbon filter 45a and two lengths of cellulose acetate 45b one on either side of carbon 45a Carbon 45a may be for example a length of activated carbon filter cut from a commercial product known as R 15243 available from American Filtrona Corp Rich mond Va USA which has circumference of about 24 7 mm Cellulose acetate 46b may be conventional cellu lose acetate such as is used in the manufacture of smok ing cigarettes Carbon filter 45a may have a length of 20 mm Each piece of cellulose acetate 46b may have a length of 5 mm and circumference of 24 7 mm 5 404 885 13 Cap 512 is a cylindrical receptacle made of a material having a low coefficient of friction with respect to the interior wall of lumen 504 e g a polyethylene material It is used to insert filter 45 into lumen 504 without dam aging the structural integrity of filter 45 and to form a press fit compressive seal between cap 512 filter 45 and the inside walis of lumen 504 Cap 512 is provided with a thickness on the order of 0 75 mm and retains filter 45 without distorting its shape Cap 512 has an open end 513 opening toward the distal end 503 that is about the same diameter as filter 45 for receiving the components of filter 45 Cap 512 also has an aperture 515 facing end 501 that is about the same diameter as the inner or outer diameter of lumen 506 The latter diameter is not criti cal except that the end of cap 512 having aperture 515 ret
47. nventionally obtained as follows m p2 pl v2 v1 8 c p1 vi p2 v1 v2 vI 9 Referring to FIG 2D a macro flow diagram of the data communication function of the apparatus is shown Initialization step 100 provides for initialization of the communications channel This channel establishes serial 5 404 885 21 RS232 communication under the industry standard x modem protocol with external devices such as porta ble computers It is used to monitor the operation of the gas analyzer and for development and diagnosis of sys tem failures Any terminal device such as a portable computer equipped with a suitable communication pro gram such as BITCOM or PROCOMM will automati cally be able to receive the data files at 9600 baud for the examination and evaluation The foregoing routines may be implemented in soft ware for controlling the described elements in a con ventional manner that is within the abilities of a person of ordinary skill in the art as set forth in the copending and commonly assigned application Ser No 07 899 261 the disclosure of which is incorporated herein by reference Implementation of the present in vention in alternate microprocessor controlled devices analog circuit controlled devices and finite state ma chines with appropriate controlling software inte grated and or discrete circuit elements and logic cir cuits is believed to be within the ability of a person of ordinary skill in the
48. oviding the interconnected second lumen tube segment and third lumen as a second gas flow path through the body and passing said sample of gas through said first consum able filtration medium 2 The method of claim 1 further comprising forming the body as an extruded tri lumen body having simulta neously coextruded first second and third lumens 3 The method of claim 2 wherein forming the body further comprises providing the first second and third lumens with walls of about the same thickness 4 The method of claim 2 wherein forming the body further comprises co extruding the first second and third lumens with respective first second and third longitudinal axes in a common plane 5 The method of claim 1 wherein providing the body further comprises providing the first second and third lumens with different inner dimensions 6 The method of claim 5 further comprising inserting a plug in one of the second and third lumens at the one end receiving the tube segment and providing an inte rior flow passageway through the plug having an inner dimension that corresponds to the inner dimension of the other of the second and third lumens wherein the inserting step further comprises inserting the tube seg ment into the plug flow passageway and the other lu men 7 The method of claim 6 further comprising provid ing said first second and third lumens and said plug with a generally circular cross section 8 The method of c
49. p 60 has sufficient power to pass the analyte gas stream therethrough Flow regulator 50 and pump 60 are inserted prefera bly in tandem as illustrated in FIG 1 into or between segments of tubing 14 to maintain a desired constant flow velocity of the analyte stream Flow regulator 50 is interposed between tubing 14e which is connected to connector 16c and tubing 14 which is connected to pump 60 Pump 60 is in turn interposed between tubing 14f and tubing 14g which is connected to carbon mon oxide detector 70 Preferably pump 60 and flow regulator 50 are ad justed so that the flow is maintained at from 40 to 60 ml min more preferably 50 ml min This provides for withdrawing continuously a gas sample either from room air or from the patient s posterior nasal pharynx depending on placement of the cannula 10 including expired and end tidal breath for patients having a breathing rate of from 10 to 90 breaths per minute The flow regulator 50 provides for limiting the flow rate of the analyte gas stream and the pump 60 provides for sampling the gas sample room air or breath such that pump 60 is driven against the flow rate limit set by flow regulator 50 This maintains a constant flow rate for the analyte stream and avoids any flow surges due to a patient s inhalation or expiration One suitable flow regulator is orifice needle valve model F 2822 41 B80 55 available from Air Logic Racine Wis which can be adjusted to obtain t
50. r measuring breath carbon dioxide CO2 and car bon monoxide CO during a second time period In the present invention before each sample is ob tained pump 60 is off for a delay time period This allows the CO detector to return to a zero state so that effectively no CO is in the sample cell When desired a supply of inert gas may be provided and pump 60 acti vated for a time to clear the sample cell of any CO and COz2 gas A three way valve and an actuator may be included not shown to achieve this cell clearing func tion The delay time period is at least about one minute more preferably three minutes In the background measurement sequence step 121 the user is prompted to place the end 11 of cannula 10 somewhere in the vicinity of the patient but not inside the nostril and then to press button 1 In response to pressing button 1 pump 60 is activated at time to and the background room air is drawn through tubing 14 and during a first time period of approximately 45 sec onds During this time display 90 preferably displays a suitable message corresponding to the duration of the background measuring test e g how much time re mains to complete the test in seconds or in percent At time t at the end of the first time period pump 60 is turned off The carbon monoxide concentration in the sample cell of the carbon monoxide detector 70 is then determined and recorded in memory as AS noted the carbon monoxide gas
51. red embodiment nor mal supply B1 is a regulated power supply derived from AC mains Alternately two 12 volt batteries e g re chargeable batteries could be used Devices Q3 and Q4 are integrated circuit regulators types LM78L05 and LM79L05 which provide 5 volts respectively for powering the interface amplifier BU1A Diodes D1 and D2 1N4148 type diodes auto matically switch to supply to the CO amplifier BUIA the greater of the normal 12 volt DC supply Bla and the backup battery B2 an alkaline 9 volt battery Device Q1 regulates the supply voltage to 5 volts Device Q2 is an integrated circuit virtual ground sup ply model TLE2425 available from Texas Instruments Dallas Tex Its output splits the five volt input into a 3 2 5 volt supply with a virtual ground at 2 5 volts DC real potential Amplifier BU1 of circuit 83 includes two type 1458 dual operational amplifiers BU1A and BU1B available from National Semiconductor Santa Clara Calif Am plifier BU1B is configured as a differential amplifier with gain of 1 and has inputs of the virtual ground from the CO amplifier circuit 82 and the CO amplifier circuit 82 output Resistors BR3 120k and capacitor BC3 10 pf provide further low pass filtering with a 1 2 second time constant Amplifier BU1A is configured as a voltage follower with a low output impedance for driving the analog input on the Little Giant microcom puter board 80 Referring to FIG 2 t
52. rst time period i e 45 seconds Initial CO and CO2 samples may be ob tained for analytical purposes During this second time period the display 90 preferably displays a suitable message corresponding to the duration of the measuring test e g how much time remains to complete the test in seconds or in percents At time t3 at the end of the second time period pump 60 is turned off During the second time period the signals corre sponding to the CO2 concentration obtained from CO2 detector 30 are acquired The relative changes in CO2 concentration over time are then used to calculate the duty cycle dc of the patient s end tidal breath Prefera bly the signal corresponding to the carbon dioxide concentration is periodically sampled e g the analog signal is digitized at a first sampling rate e g 30 Hz during the second time period These samples are stored in a data buffer for post data acquisition processing and analysis Also the signals corresponding to the CO concentra tions obtained from detector 70 are acquired during the second time period Preferably the carbon monoxide concentration is periodically sampled e g the analog signal is digitized at a sampling rate of 1 0 Hz during the second time period These samples also are stored in the data buffer for analysis FIGS 3a and 3b illustrate representative sampled waveforms of the signals and provided by the CO and CO detectors 70 and 30 respectively d
53. sensitivity variations in gas de tectors Amplifier U3B also has a secondary input from amplifier U1A which is configured as an adjustable 10 15 40 45 55 60 65 10 voltage source that may be used to compensate for a zero gas output of detector 70 Amplifier U3A is configured as a unity gain buffer designed to isolate the previous stages from any load effects that may be imposed by following circuitry Amplifier U2A is configured as shown as an adjust able bias source for the counter electrode of detector 70 as determined by the setting of resistor R21 a 500kQ potentiometer A 10k resistor R22 provides a means of reading the bias voltage without making direct contact with the gas detector connections The CO detector amplifier circuit 82 operates as a low power supply voltage to prevent excess leakage currents from impos ing undesirable bias currents on the detector 70 and to allow low power continuous biasing of the detector 70 to allow for stable operation Preferably amplifiers U2A and U3A also are type OP 290 amplifiers In the circuits illustrated in FIGS 2E and 2F all ground con nections are to a virtual ground which is provided by a CO amplifier power supply circuit 83 Referring to FIG 2F the CO amplifier power supply and interface circuit 83 is shown The power supply consists of a normal supply B1 and a backup supply B2 Normal supply B1 may be any nominal 12 volt DC power supply In one prefer
54. sonnel to transport the sample from the patient to the laboratory or equip ment where the analysis is conducted and then to report back to the attending physician practitioner for a diagnosis and prescription if any Another problem with this technique is that accurate assessment of the concentration difference in carbon monoxide requires obtaining good samples of end tidal patient breath This essentially requires that the patient have a regular predictable breathing cycle Thus it can be difficult to obtain a good sample by watching chest wall movement particularly for a newborn and for patients having irregular breathing cycles Chemical electrochemical sensors capable of measur ing carbon monoxide concentrations in the range of interest 0 to 500 parts per million ppm are commer cially available e g model DragerSensor CO available from Dragerwerk Lubeck Germany However such sensors are sensitive to many other gases as well as carbon monoxide and are therefore susceptible to er ror Another problem with such sensors is that the mea surement dynamics of the sample gas transport through the gas permeable membrane and oxidation reduction in the electrochemical cell results in a relatively slow response time such that discrete samples of the end tidal breath must be obtained and analyzed to determine the end tidal carbon monoxide concentration SUMMARY OF THE INVENTION It is therefore an object of the present invention
55. t ment of the condition by an appropriate remedy and for monitoring the efficacy of the treatment BRIEF DESCRIPTION OF THE DRAWINGS The above and other objects and advantages of the invention will be apparent upon consideration of the following detailed description taken in conjunction with the accompanying drawings in which like refer 5 404 885 5 ence characters refer to like parts throughout and in which FIG 1 is a schematic block diagram of an apparatus for determining end tidal carbon monoxide concentra tion in accordance with the present invention FIG 2 is a diagram of a multipurpose microcon troller board for controlling the device in FIG 1 FIGS 2A 2D are macro flow diagrams for the over all breath measurements calibration and data commu nication operations of the apparatus of FIG 1 FIGS 2E and 2F are circuit schematic diagrams for a signal conditioning amplifier and a power supply re spectively for interfacing the carbon monoxide sensor of FIG 1 and the microcontroller circuit board of FIG 2 FIGS 3A and 3B are graphical illustrations of mea surements of carbon monoxide and carbon dioxide con centrations acquired using the device of FIG 1 FIGS 4A and 4B are graphical illustrations of the carbon monoxide and carbon dioxide concentrations in a representative breath flow FIG 5 is an elevated perspective view of a filter unit in accordance with a preferred embodiment of the in vention FI
56. to derive the end tidal carbon monoxide concentration in real time More particularly a conventional carbon monoxide detector can be used to obtain the average carbon monoxide concentration level during breathing which average value can be related to the end tidal value based on the determined Tatio of end tidal to inspired breath Preferably the most common interfering substances from a sampled breath are removed from the sample by a consumable filtration medium so that these substances do not affect the measurement The present invention also applies to gas components of exhaled breath other than carbon monoxide which gas components cannot be directly monitored because of the slow response time of avail able gas detectors One aspect of the present invention concerns using a second gas component of the breath other than the first gas component whose concentration is being moni tored to determine the ratio of the end tidal breath to inspired air The relative concentration level of the second gas during respiration is monitored and the ratio or duty cycle of the end tidal portion of the sensed concentration waveform relative to the inspired air is determined A sensor for detecting the level or concen tration of the second gas having a time response that is fast enough to distinguish the end tidal breath concen tration from the inspired air is preferably used One suitable gas component is carbon dioxide which has a large distinctiv
57. uring a second time period The waveforms thus display the concentration levels sensed corresponding to the cali brated CO and 02 levels In these representative drawings the calibration functions were CO ppm 12 11 Ve9 0 95 and 5 10 15 20 25 30 35 45 50 55 65 18 CO2 11 96 0 The calculated duty cycle de was 42 30 the COkgr was 2 10 ppm the CO oom was 2 01 ppm the veo was 0 78 v and the vco 1 was 0 088 v The veo min was 0 05 v and the Veo max was 0 17 v corresponding also to the start t2 and stop t3 measurement voltages The maximum was about 0 42 volts The 30 Hz sampling rate of CO2 was selected because it corresponds to the anatomical waveform of respira tion from which the ratio of the end tidal portion total air can be derived The CO sensor time response of 120 ms gives adequate resolution without acquiring exces sive data The sampling rate of 1 Hz for the CO detector voltage was selected because the CO detector has a much slower response time the half time of the CO response is about ten seconds which cannot discrimi nate the end tidal portions and room air Sampling at a higher rate would not significantly improve the data resolution The selected rates were selected as compro mises between collecting sufficient data with adequate resolution in view of the sensor response time and may be changed according to the sensors used and the par t
58. y breathing pa tient e g an infant End 11 has at least one aperture 12 for extracting a sample of the exhaled breath as de scribed below Preferably end 11 has a length and an inner and outer diameter appropriate for insertion into the patient s nostril e g a 3 0 cm length of tubing hav ing an inner diameter on the order of 1 0 to 1 5 mm and an outer diameter of 2 3 mm and a sufficient number of holes 12 perforating the tube circumference for receiv ing a sample of breath The dimensions may be adjusted for the size of the patient The length of cannula 10 is 5 10 15 20 25 30 35 40 45 50 55 60 65 6 sufficient to extend from the base 5 to the patient and is typically on the order of 75 to 100 cm Segments of tubing 14a 140 14c 14d 14e 14f and 14g are used to form the flow path between the various elements of the apparatus as shown in FIG 1 The tube segments may be made of for example medical grade catheter tubing polyethylene polypropylene or vinyl The ends of the segments are typically frictionally fitted over bosses of connectors 16 and the various compo nents as shown in FIG 1 and may be clamped for a more secure interconnection Connectors 16a 16b and 16c are preferably mounted in the same region of base 5 to allow for easy access for replacement of the cannula and filters Cannula 10 is connected at its other end in series with filter 15 connector 16a a second length of
59. ydrogen Test In Infants The Lancet vol 337 pp 90 93 Jan 12 1991 Product Literature Z World Engineering Little Giant Miniature Microcontroller One page Product Literature Servomex Mode 1505 Co2 Infra eS a aT eas ae kL LLL MALLA M a A A sa red Transducer brochure 2 pages and technical note 9 pages Product Literature KNF Diaphragm Micro Pump Type NMP 02 2 pages Primary Examiner Lee S Cohen Assistant Examiner Robert L Nasser Jr Attorney Agent or Firm Davis Hoxie Faithfull amp Hapgood 57 ABSTRACT A noninvasive device and methods for measuring the end tidal carbon monoxide concentration in a patient s breath particularly newborn and premature infants The patient s breath is monitored An average carbon monoxide concentration is determined based on an av erage of discrete samples in a given time period The ratio of the end tidal portion of the breath flow sample is separately determined preferably based on monitor ing the level of carbon dioxide in the gas sample and identifying the carbon dioxide concentration levels cor responding to the end tidal portion of the breath sam ple The sensed carbon monoxide level is converted to the end tidal carbon monoxide level by subtracting the ambient carbon monoxide level and dividing the re mainder by the ratio of end tidal breath to breath in the breath sample An easy to use microcontrol

@?igllalgiill —

Contents

Download Pdf Manuals

Related Search

Related Contents

@?igllalgiill &mdash;

Contents

Download Pdf Manuals

Related Search

Related Contents

@?igllalgiill —