Methods, apparatus and systems for monitoring CO2

Abstract

There is provided herein methods, apparatus and systems for evaluating carbon dioxide (CO.sub.2) concentration in a subject's breath, for example in subjects ventilated with High Frequency Ventilation (HFV), the method includes inserting to a trachea of a subject an endotrachial tube (ETT), sampling breath from an area in the trachea located in proximity to a distal end of the endotrachial tube (ETT) and evaluating one or more CO.sub.2 related parameters of the sampled breath.

Claims

1. A method for detecting spontaneous breaths in a subject ventilated with high frequency ventilation (HFV) using a capnograph, the method comprising: ventilating the subject with HFV, wherein the ventilating comprises providing respiratory gas through a ventilation lumen of an endotracheal tube (ETT); monitoring a level of carbon dioxide (CO.sub.2) in a breath of the subject, wherein the monitoring comprises: repeatedly sampling breath from a distal area of a trachea of the subject through a sampling lumen of the endotracheal tube (ETT) over a rolling time window during ventilation, wherein the sampling lumen is separate from the ventilation lumen and comprises a distal opening that is open to the distal area and proximate to a distal end of the ETT; thereby substantially preventing mixing of the sampled breath with inhaled air; measuring a CO.sub.2 related parameter of the sampled breath via a CO.sub.2 sensor coupled to the sampling lumen to determine CO.sub.2 concentrations of each sampled breath at a plurality of time points in the rolling time window based on the measured CO.sub.2 related parameter; using a processor of the capnograph to determine over the rolling time window: a continuous CO.sub.2 (Con.CO.sub.2) value in the sampled breath using an average of the CO.sub.2 concentrations; and an instantaneous CO.sub.2 concentration value in the sampled breath using a CO.sub.2 concentration from a single time point during the rolling time window; identifying, using the processor, spontaneous breathing when the instantaneous CO.sub.2 concentration measured deviates from the determined Con.CO.sub.2 value by a predetermined threshold value; displaying the Con.CO.sub.2 value and the identified spontaneous breathing on a display; and providing instructions to stop updating the displaying of the Con.CO.sub.2 value when the spontaneous breathing is identified and continue displaying the Con.CO.sub.2 value associated with the identified spontaneous breathing until no spontaneous breathing is identified.

2. The method of claim 1, wherein a spontaneous breath is identified when the instantaneous CO.sub.2 concentration deviates from the Con.CO.sub.2 value by the predetermined threshold value for a predetermined period of time.

3. The method of claim 1, further comprising computing a density of spontaneous breaths.

4. The method of claim 1, wherein the time window is continuously updated.

5. The method of claim 1, wherein the subject is a child, an infant, and/or a neonate.

6. The method of claim 1, wherein the Con.CO.sub.2 value is displayed graphically and wherein the identified spontaneous breathing is superimposed on the graphically displayed Con.CO.sub.2 value.

7. The method of claim 6, wherein the Con.CO.sub.2 value is displayed as a waveform having a sweep rate slower than a rate of HFV.

8. The method of claim 1, wherein the sampling lumen is coupled to the CO.sub.2 sensor via a valve, and comprising providing instructions to a controller to open the valve at the plurality of time points.

9. The method of claim 8, comprising providing instructions to the controller to close the valve when the spontaneous breathing is identified and comprising freezing determining the Con.CO.sub.2 value when the spontaneous breathing is identified.

10. The method of claim 1, wherein the CO.sub.2 sensor is an optical sensor, and wherein the CO.sub.2 concentrations are determined based on detected light returned through the sampling lumen.

11. The method of claim 1, displaying an error message associated with the Con.CO.sub.2 value or stopping display of the Con.CO.sub.2 value when the spontaneous breathing continues for greater than a predetermined time.

Description

BRIEF DESCRIPTION OF FIGURES

(1) Examples illustrative of embodiments of the invention are described below with reference to figures attached hereto. In the figures, identical structures, elements or parts that appear in more than one figure are generally labeled with a same numeral in all the figures in which they appear. Dimensions of components and features shown in the figures are generally chosen for convenience and clarity of presentation and are not necessarily shown to scale. The figures (FIGs.) are listed below.

(2) FIG. 1A-C schematically show double lumen Endotrachial Tubes (ETTs), according to some embodiments;

(3) FIG. 2 shows an example of a capnograph display, according to some embodiments;

(4) FIG. 3 A and B show the linear correlation between distal EtCO.sub.2 (dEtCO.sub.2) (A) and proximal EtCO.sub.2 (pEtCO.sub.2) (B) and arterial CO.sub.2 (PaCO.sub.2), according to some embodiments;

(5) FIGS. 4A and B present the Bland-Altman plots of the differences between distal EtCO.sub.2 (dEtCO.sub.2) (A) and proximal EtCO.sub.2 (pEtCO.sub.2) (B) and arterial CO.sub.2 (PaCO.sub.2), according to some embodiments; and

(6) FIG. 5 shows the linear correlation between distal EtCO.sub.2 (dEtCO.sub.2) and arterial CO.sub.2 (PaCO.sub.2) in subjects ventilated with High Frequency Ventilation (HFV), according to some embodiments.

DETAILED DESCRIPTION OF EMBODIMENTS

(7) In the following description, various aspects of the invention will be described. For the purpose of explanation, specific configurations and details are set forth in order to provide a thorough understanding of the techniques. However, it will also be apparent to one of skill in the art that the techniques may be practiced without specific details being presented herein. Furthermore, well-known features may be omitted or simplified in order not to obscure the description(s) of the techniques.

(8) According to some embodiments, sampling breath for CO.sub.2 monitoring may be performed from a position much closer to the bronchial tube (at the lower section of the trachea) than the current sampling position. This type of CO.sub.2 sampling and evaluation may also be referred to as a distal CO.sub.2 measurement. As discussed hereinabove, the current sampling configuration is problematic since it involves sampling from an area close to subject's mouth and to the proximal end of the ETT, wherein CO.sub.2 is mixed with ventilated air, which eventually leads to erroneous CO.sub.2 readings. It was found that sampling breath from a position closer to the bronchial tube (distal CO.sub.2 measurement) may be less susceptible to air leak and/or mixing of the measured CO.sub.2 with inhaled air. More particularly, sampling breath for distal CO.sub.2 measurement may be performed at the distal end of the ETT which is adapted to be positioned inside the bronchial tube. According to some embodiments, sampling breath for distal CO.sub.2 measurement may be performed by inserting a catheter into the ETT, wherein the catheter is adapted to sample CO.sub.2. The catheter may, however, partly occlude or add resistance to the airway. According to some preferred embodiments, sampling breath for distal CO.sub.2 measurement may be performed through the distal part of what is known as a double lumen Endotrachial Tube (ETT). Double lumen ETTs have been used so far as a means for suctioning and administration of surfactants and similar agents. The second (extra) lumen is typically a very small diameter tube which runs within the wall of the first lumen from about half way down to a point close to the distal exit of the ETT.

(9) Reference is now made to FIG. 1A which schematically shows a double lumen Endotrachial Tube (ETT), according to some embodiments. Endotrachial Tube (double lumen ETT) 100 includes a main endotrachial tube 102 having a larger diameter and a small diameter tube 104 (for example, approximately 0.8 mm) located essentially inside and along the wall of main endotrachial tube 102. Small diameter tube 104 has a distal opening 106 a few millimeters before the distal end 108(towards the subject's bronchial tube and lungs) of ETT 100. Small diameter tube 104 also includes, at its end opposing distal opening 106, a second opening having a connector 110, adapted to connect to or allow access to suction devices and/or to allow application of agents such as surfactants, medications or the like. According to some embodiments of the invention adapter 110 may be adapted to connect to a sampling line for sampling CO.sub.2 in exhaled breath from distal end 108 of ETT 100 through small diameter tube 104. Proximal opening 130 of main endotrachial tube 102 is adapted to connect to a ventilator.

(10) According to some embodiments, sampling breath for CO.sub.2 monitoring is performed from the area of the distal end (such as distal end 108) of the double lumen EET (such as double lumen ETT 100). The sampling is performed through the small diameter tube (such as small diameter tube 104) of the double lumen ETT.

(11) Tests clearly showed that for subjects with and without High Frequency Ventilation (HFV) (adults, children, infants and/or neonates) distal CO.sub.2 measurement performed, for example through a double lumen ETT, produced a significantly better or at least comparable correlation and agreement with arterial CO.sub.2. For example, better correlation was obtained between distal EtCO.sub.2 (dEtCO.sub.2) with arterial CO.sub.2 (PaCO.sub.2) than the correlation of pEtCO.sub.2 measured by mainstream or sidestream capnograph sampling at the subject airway proximally with arterial CO.sub.2 (PaCO.sub.2).

(12) Sampling at the distal point of the ETT in subjects and particularly in neonates has another issue: there are many fluids at the distal point. According to some embodiments, in order to solve or reduce the fluid problem and prevent them from reaching the analyzer, a fluid reducing device may be used.

(13) The fluid reducing device may include a standard airway adapter and sampling connector to the sampling line having a stop-cock type valve allowing in its first position to sample breath and in its second position to close the sampling line and open an opening for suction of fluids from the distal section of the trachea.

(14) According to some embodiments, it may be beneficial if the breath sampling opening of the double lumen is several millimeters inside the endotrachial main tube, with possibly several small apertures (hence, if one aperture is covered with fluids, the sampling will continue through one of the remaining openings).

(15) Reference is now made to FIG. 1B which schematically shows a double lumen Endotrachial Tube (ETT), according to some embodiments. Endotrachial Tube (double lumen ETT) 200 includes a main endotrachial tube 202 having a larger diameter and a small diameter tube 204 (approximately 0.8 mm) located inside and along the wall of main endotrachial tube 202. Small diameter tube 204 has a distal opening 206 a few millimeters before the distal end 208 (towards the subject's bronchial tube and lungs) of ETT 200. Distal opening 206 of small diameter tube 204 has several (in this case three) additional apertures 209. When one or more of apertures 209 is blocked with fluids, the sampling will continue through one or more of the remaining openings.

(16) Small diameter tube 204 also includes, at its end opposing distal opening 206, a second opening having a connector 210. Connector 210 includes a connecting element 211 adapted to connect to small diameter tube 204. Connector 210 further includes a sampling opening 212 adapted to connect to a sampling line 214, optionally with drying tube 216 adapted to absorb and/or pervaporate fluids present in the sampled breath. Connector 210 also includes suction port 218 through which suction of fluids from the distal section of the trachea can be performed. Suction port 218 may also be adapted to allow application of agents such as surfactants, medications or the like. Connector 210 further includes valve 220. Valve 220 has two optional positions, a first position (as shown in FIG. 1B) allows the flow of air sampled through small diameter tube 204 to drying tube 216 and sampling line 214 and on to the analyzer (such as a capnograph). The second position (not shown) of valve 220 approximately perpendicular to the first position. In the second position, valve 220 blocks the flow of air sampled through small diameter tube 204 to drying tube 216 and sampling line 214 and allow the flow towards suction port 218.

(17) Valve 220 (or any other valve) may be adjusted by a user to allow sampling and from time to time, as needed or every period of time, allow suction or application of medication while blocking the sampling path. Proximal opening 230 of main endotrachial tube 202 is adapted to connect to a ventilator. Valve 220 (or any other valve) may also be automatically adjusted by a controller to allow sampling and every period of time trigger suction or application of medication while blocking the sampling path. The controller may also be adapted to stop the sampling pump upon blocking the sampling line.

(18) According to embodiments of the invention, the connector (such as connector 210) may be integrally formed with the second endotrachial tube, which may also be referred to as small diameter endotrachial tube (such as small diameter tube 204), or may be adapted to be (removably or permanently) affixed or mounted on the proximal end of the second endotrachial tube.

(19) According to some embodiments, sampling breath for CO.sub.2 monitoring is performed from the area of the distal end (such as distal end 208) of the double lumen EET (such as double lumen ETT 200). The sampling is performed through the small diameter tube (such as small diameter tube 204) of the double lumen ETT.

(20) For clarification and the avoidance of doubt, a double lumen ETT or double lumen endotrachial tube includes an endotrachial tube with two or more lumens. The two or more lumens may have the same or different internal diameters.

(21) The fluid reducing device may also include a drying tube, such as but not limited to a Nafion tube or any other drying tube. In case of standard ventilation (where the waveform is analyzed) particularly in infants and neonates, it should be noted that using standard larger water traps, collectors, filters or the like may add extra dead space or minor interference to the breath flow which may effect the waveform.

(22) In case of HFV it may be possible to add filter(s), liquid trap(s), dryer tubes or the like, since in HFV mode response time is less critical compared to standard ventilation, though its (their) size may dampen somewhat the spontaneous breaths.

(23) According to some embodiments, one or more of the small diameter tubes of double-lumen ETTs (such as small diameter tubes 104 and 204) may be used for insertion of a sensor or a detector adapted to reach approximately the distal section of the trachea and sense (detect) breath elements such as CO.sub.2. This may replace sampling or conducted in addition to sampling. Such sensor can be a chemical sensor, electronic sensor, optic sensor or any other sensor/detector. For example, the small diameter tubes of a double-lumen ETT may be adapted to receive a fiber optics adapted to transmit and return radiation (for example IR radiation at a wavelength that CO.sub.2 absorbs), and thus detect one or more breath parameters (such as CO.sub.2 levels or waveforms in case of standard ventilation). In another embodiment, radiation (such as light) may be emitted through the main endotrachial tube (such as main endotrachial tubes 102 and 202) in such way that light entered through the main endotrachial tube is reflected by an appropriate reflector back through an optical fiber in the small diameter tube back to an appropriate detector.

(24) According to some embodiments, there is also provided an ETT, having a main endotrachial tube and a second endotrachial tube (optionally having a smaller diameter than the main endotrachial tube). The second endotrachial tube is located outside the main endotrachial tube (as apposed to inside of the main endotrachial tube as shown above). The distal opening of the second endotrachial tube may be in proximity to the distal opening of the main endotrachial tube but may also be shorter, such that upon insertion to the trachea, it only would only reach the cavity of the mouth for sampling exhaled air that escaped around the uncuffed ETT. This second line may also (as above) connect by a stop-cock to the main (neonatal) sampling adapter. A user could toggle between the two sampling points.

(25) According to some embodiments, the main endotrachial tube may include, at or in proximity to its distal end, a mechanism that is adapted to open when positive pressure from a ventilator pushes in the air for ventilation, while close on exhalation. This way, the exhaled breath will be forced to return around the outside of the main endotrachial tube to be collected by the second endotrachial tube. It is noted however, that a mechanism such as mechanism 340 may apply to standard ventilation, while, in HFV where the main concept is base on diffusion, such mechanism may not be applicable.

(26) Reference is now made to FIG. 1C which schematically shows a double lumen Endotrachial Tube (ETT), according to some embodiments. Endotrachial Tube (double lumen ETT) 300 includes a main endotrachial tube 302 and a second endotrachial tube 304 located outside and along the wall of main endotrachial tube 302. Second endotrachial tube 304 has a distal opening 306 at approximately one third of the way of main endotrachial tube 302, so that upon insertion to the trachea, it only would only reach the cavity of the mouth for sampling exhaled air that escaped around uncuffed ETT 300.

(27) Second endotrachial tube 304 also includes, at its end opposing distal opening 306, a second opening having a connector 310. Connector 310 includes a sampling opening 312 adapted to connect to a sampling line 314. Connector 310 also includes suction port 318 through which suction of fluids from the distal section of the trachea can be performed. Suction port 318 may also be adapted to allow application of agents such as surfactants, medications or the like. Connector 310 further includes valve 320. Valve 320 has two optional positions, a first position (as shown in FIG. 1C) allows the flow of air sampled through small diameter tube 304 to sampling line 314 and on to the analyzer (such as a capnograph). The second position (not shown) of valve 320 approximately perpendicular to the first position. In the second position, valve 320 blocks the flow of air sampled through small diameter tube 304 to sampling line 314 and allow the flow towards suction port 318. Valve 320 (or any other valve) may be adjusted by a user to allow sampling and from time to time, as needed or every period of time, allow suction or application of medication while blocking the sampling path. Proximal opening 330 of main endotrachial tube 302 is adapted to connect to a ventilator. Valve 320 (or any other valve) may also be automatically adjusted by a controller to allow sampling and every period of time trigger suction or application of medication while blocking the sampling path. The controller may also be adapted to stop the sampling pump upon blocking the sampling line.

(28) Main endotrachial tube 302 also includes, in proximity to its distal end 308, a mechanism 340 that is adapted to open when positive pressure from a ventilator pushes in the air for ventilation, while close on exhalation. It is noted however, that a mechanism such as mechanism 340 may apply to standard ventilation, while, in HFV where the main concept is base on diffusion, such mechanism may not be applicable. This way, the exhaled breath will be forced to return around the outside of the main endotrachial tube to be collected by the second endotrachial tube.

(29) According to some embodiments, a miniature nano-technology CO.sub.2 sensor may be placed in the trachea through the small diameter tube of the double lumen ETT. This configuration may allow measuring the CO.sub.2 in-situ. According to other embodiments, the CO.sub.2 nano sensor can also be placed in any ETT not necessarily double lumen ETT. Similarly, any other sensor, such as an O.sub.2 sensor may also be placed in (and/or through) the small diameter tube of the double lumen ETT or any ETT in addition or instead of the CO.sub.2 nano sensor. According to some embodiments, the sensor may be disposable.

(30) High Frequency Ventilation (HFV):

(31) Additional or alternative embodiments of the invention are generally directed to a method and apparatus for using capnography in monitoring breath carbon dioxide (CO.sub.2) in subjects, particularly, but not limited to, small children and infants, who are ventilated by High Frequency Ventilation (HFV) technique.

(32) As discussed above when considering capnography for replacing at least some of the blood gas samples, and in general to provide continuous monitoring for HFV (such as HFOV) mode of ventilation, some difficulties arise. These difficulties include very high ventilation frequencies, lack of clear, textbook breath cycle and when sampling at the standard position for capnography, either in mainstream or sidestream, the CO.sub.2 concentration is much lower than what is really occurring in the lungs.

(33) According to some embodiments of the invention, there are provided a method and apparatus for CO.sub.2 sampling and monitoring in subjects (for example, but not limited to, children, infants, and neonates) ventilated by the HFV mode while overcome issues related to difficulties such as those discussed herein.

(34) According to some embodiments of the invention, since in HFV one can expect long periods without observing typical waveforms and breath cycles, which are not the result of apnea, the platform for CO.sub.2 sampling in HFV subjects should take this into account or be insensitive to such instances.

(35) New Parameters to be Provided to the User:

(36) This following describes, according to some embodiments of the invention, possible requirements, improvements and/or changes needed in order to provide an appropriate Capnography mode of operation with subjects ventilated with HFV.

(37) According to some embodiments, there are provided new parameters for defining HFV mode. These parameters may optionally have their own alarm management and trend characteristics. Of course, the names given to these parameters are not binding and are only optional.

(38) According to some embodiments, the following parameters may be defined and used for capnography in subjects ventilated with HFV. Some of these parameters may be used instead of or in addition to standard respiratory rate (RR), EtCO.sub.2 parameters or other known standards. a) Cont.CO.sub.2Continuous CO.sub.2: According to some embodiments, this is a main value used in HFV capnography and can be calculated as the average CO.sub.2 reading (concentration) over the last x seconds (which could be 5 seconds or 1 to 60 seconds or any other period), updated every y second (y could be 1 to 60 seconds or any other period). If within this period a spontaneous breath is detected or even the possible beginning of such a breath is suspected (to be defined in section e below), then the last Cont.CO.sub.2 value could be frozen until a new period (such as, a 5-second period) has passed without any identified spontaneous breath. If the spontaneous breaths continue for more than possibly z seconds (such as, 60 seconds) without a w second (for example, 5 second) gap, the Cont. CO.sub.2 value may be determined and optionally displayed as invalid (for example a dash is provided in place of the value). b) S-EtCO.sub.2Spontaneous EtCO.sub.2: If a spontaneous breath cycle (to be defined in section e below) is recognized (typically a result of spontaneous breathing), then, according to some embodiments, the highest CO.sub.2 (concentration) value of the breath, S-EtCO.sub.2 (Spontaneous EtCO.sub.2), may be measures and optionally displayed. The displayed value may be the highest result that was collected over the last m seconds (possibly 1 to 60 seconds). Again, it may be updated every period of time (once a second for example). If for n seconds (for example, 20 seconds) there is no new breath, the S-EtCO.sub.2 value may be determined and optionally displayed as invalid (for example a dash is provided in place of the value). c) S-FiCO.sub.2Spontaneous fractional concentration of final inspired CO.sub.2: If a breath cycle is recognized, then, according to some embodiments, the lowest CO.sub.2 (concentration) value in the breath cycle (Spontaneous fractional concentration of final inspired CO.sub.2, S-FiCO.sub.2) may be used and the value obtained and optionally displayed being the lowest collected over the last u seconds (possibly 1 to 60 seconds). Again, it may be updated every period of time (once a second for example). If for t seconds (for example, 20 seconds) there is no new breath, the S-EtCO.sub.2 value may be determined and optionally displayed as invalid (for example a dash is provided in place of the value). d) DCO.sub.2Diffusion (gas transport coefficient) CO.sub.2 DCO.sub.2: This parameter may be similar to the conventional ventilation parameter that is the product of tidal volume and frequency, known as minute ventilation, which aptly describes pulmonary gas exchange. The gas transport coefficient which defines the CO.sub.2 elimination correlates to the product of oscillatory volume squared and the frequency. For this purpose, it would be necessary to enable entering of the HFV ventilator parameters into the Capnograph. e) Inst. CO.sub.2Instantaneous CO.sub.2: a raw unprocessed measurement of CO.sub.2, According to some embodiments, every period of time (for example, once every 50 msec, a CO.sub.2 measurement is performed). If the measured CO.sub.2 change of at least c mmHg (c can for example be between 1 and 10 mmHg) above (or below) the Cont.CO.sub.2 current (latest) value and lasting for at least k milliseconds, msec (for example, 200 msec), a spontaneous breath is suspected. The system may trace for a peak to peak (PTP) of c mmHg lasting more than a minimal k period, for example 200 msec. During this stage the Cont.CO.sub.2 value may be frozen as stated above. In case of a timeout (of for example, 3 seconds) with no c mmHg PTP, the PTP trace may be stopped and the Cont.CO.sub.2 calculation may be resumed. A spontaneous breath is counted every 2 consecutive occurrences of c mmHg PTP. f) Low CO.sub.2: Since in HFV one can expect long periods without observing a typical waveforms and breath cycles, there is no meaning to the term apnea or no breath, hence the term low CO.sub.2 may be used instead. g) High and low Cont. CO.sub.2 alarms: According to some embodiments, the alarms relating to RR, high and low EtCO.sub.2 may be disabled and Cont. CO.sub.2 high and low may be enabled. h) Density of spontaneous breaths: According to some embodiments the Density of spontaneous breaths may be calculated. This value may be obtained by calculating what percentage of the time the subject is spontaneously breathing i) According to some embodiments, trends of any CO.sub.2 related parameter (such as Cont. CO.sub.2 may be provided and optionally presented as a graph or table that demonstrates the change of the parameter over time. j) According to some embodiments, the Cont. CO.sub.2 value may be displayed at a position where in normal mode (non-HFV) the EtCO.sub.2 value is displayed. The other two parameters (S-EtCO.sub.2 and FiCO.sub.2) may be displayed where in normal mode (no-HFV) the RR and FiCO.sub.2 are displayed. k) According to some embodiments, the display may include two parts: 1) A main waveform display having a sweep rate which is slower than the standard ventilation (non-HFV) generally in the range of 0.1 to 10 mm/second. This mode displays the Continuous (Cont. CO.sub.2) with the sporadic spontaneous breaths superimposed on it. An example of a main waveform display can be seen in the top graph of FIG. 2, which shows an example of a capnograph display of a subject ventilated by HFV, according to some embodiments. The top graph shows the values of Cont. CO.sub.2 in mmHg over time (seconds, sec). The sections of the graph having clear dips indicate spontaneous breathing. 2) A display having a slower sweep rate than that of the main waveform display (section 1 hereinabove), for example in the range of 0.1 to 10 mm/min. This slower display shows the trend of the Continuous (Cont. CO.sub.2), or in other words, how the Cont. CO.sub.2 is changing over a period of time (for example, 90 min). This type of data may reduce or even eliminate the use of blood gas, since, for example, just by looking at it the doctor may know if the CO.sub.2 level is improving since the last blood gas test obtained from the subject. An example of such a trend display can be seen in the bottom graph of FIG. 2, which shows the trend of Cont. CO.sub.2 in mmHg over time (minutes, min). In addition to these graphs, values of Cont. CO2, S-EtCO.sub.2, S-FiCO.sub.2 as well as SpO2 and PR (pulse oximetery) may also be presented. l) According to some embodiments, there is provided a means for manually (or automatically) entering an event mark, for example, defining a blood gas. A red spot, for example, or similar (possibly a sigh, a letter or a combination of letters such as b.g.) may be placed on the slower trend display so that the doctor can easily see trends of CO.sub.2 relative to the last blood gas time. It is preferred that one could also add the values of the blood gas in any form (values, graphical etc.) so that they can be displayed on the trend with the sampled CO.sub.2 values.

(39) According to some embodiment of the invention, the term distal or distal end may refer to a position located (or adapted to be located) towards a subject's lungs.

(40) According to some embodiment of the invention, the term proximal or proximal end may refer to a position located (or adapted to be located) towards a subject's mouth.

(41) According to some embodiment of the invention, the term main endotrachial tube may refer to a part of an endotracheal tube through which ventilation may be performed.

(42) According to some embodiment of the invention, the term second endotrachial tube may refer to a part of an endotracheal tube which is not directly used for ventilation. A second endotrachial tube may be smaller in diameter than the main endotrachial tube. A second endotrachial tube may be integrally formed with the main endotrachial tube or connected thereto.

(43) According to some embodiment of the invention, the term sampling line or breath sampling line may refer to any type of tubing(s) or any part of tubing system adapted to allow the flow of sampled breath, for example, to an analyzer, such as a capnograph. The sampling line may include tubes of various diameters, adaptors, connectors, valves, drying elements (such as filters, traps, trying tubes, such as Nafion and the like).

EXAMPLES

Example 1

Correlation between Sampling through a Double Lumen ETT and Blood Gas

(44) Study Design

(45) A prospective observational study was conducted at Bnai-Zion Medical Center, Haifa, Israel. Infants were connected simultaneously to proximal and distal EtCO.sub.2 monitors, and the measurements were compared to PaCO.sub.2 drawn for patient care. Measurements of distal EtCO.sub.2 (dEtCO.sub.2) were not used for patients' clinical care. The study was approved by the institutional review board. All the parents signed an informed consent prior to participating in the study.

(46) The primary outcome measure was to evaluate the accuracy and the correlation of Microstream dEtCO.sub.2 with the gold standard of PaCO.sub.2. The secondary outcome measure was to compare these findings to the more standard and commonly used method of mainstream pEtCO.sub.2.

(47) Study Population

(48) Included in the study were all intubated infants in the NICU during the study period, who had the double lumen endotracheal tubes (ETT) and that their parents signed an informed consent. Excluded were infants with a single lumen endotracheal tube.

(49) All infants who needed an ETT were intubated in the delivery room or in the NICU by a double lumen tube (Uncuffed Tracheal Tube, Mallinckrodt Inc., Chih, Mexico). This ETT has an extra small lumen for administration of exogenous surfactant or for measurements of distal pressures close to the carina. In this study this side port was used to measure dEtCO2 only.

(50) Intubated infants were monitored by the two capnograms simultaneously. The side-stream dETCO.sub.2 was measured distally by a Microstream capnograph via a Microstream cannula (Oridion Medical Inc., Needham, Mass.). The main-stream pETCO.sub.2 was measured via capnogram connected to the proximal end of the ETT (Philips IntelliVue patient monitor, Capnography Extension M3014A, Philips, Boeblingen, Germany). Readings from the two methods were charted at the time of blood sampling for routine patient care via an indwelling arterial line and compared to PaCO.sub.2 level (Omni AVL, Roche Diagnostic Gmbh, Graz, Austria). Before each blood sampling it was assured that an adequate reading of pEtCO.sub.2 and a reliable waveform on the Microstream capnograph (continuous steady waveform of expired CO.sub.2 throughout the ventilatory cycle), and cleared secretions from the side port of the ETT for dEtCO.sub.2 measurement (by inserting 5 ml of air). Microstream cannulas blocked by secretions were replaced as needed.

(51) Data on the patients' characteristics, type of their pulmonary or cardiac disease and the severity of pulmonary disease (by oxygenation index defined as fractional inspired of oxygen [FiO.sub.2] X mean airway pressure/PaO.sub.2 and by the level of ventilation perfusion mismatch assessed by PaO.sub.2/PAO.sub.2 ratio) was collected. Severe lung disease was defined as: PaO.sub.2/PAO.sub.2 ratio<0.3 (18, 19) or OI>10; mild-moderate lung disease: PaO.sub.2/PAO.sub.2 ratio>0.3 and OI<10 (PAO.sub.2 was calculated by: FiO.sub.2 X [Barometric pressure47]PaCO.sub.2/0.8]. PaCO.sub.2 was assumed the same as alveolar PACO.sub.2.

(52) A bias 5 mmHg was considered a low bias and >5 mmHg a high bias (9, 10).

(53) The consistency of EtCO.sub.2 monitoring (proximal and distal) within each patient was assessed by examining the relationship between the change in PaCO.sub.2 and the change EtCO.sub.2 in consecutive samples.

(54) Statistical Analysis

(55) The correlation of distal and proximal EtCO.sub.2 and PaCO.sub.2 was evaluated by linear regression analysis and assessed the agreement between these measurements (bias [mean difference] and precision [standard deviation of the differences]) by the Bland-Altman technique (22).

(56) The correlation between the changes in PaCO.sub.2, and the simultaneous changes in proximal and distal EtCO.sub.2 were evaluated for consecutive measurements within each patient by linear regression analysis.

(57) Level of significance was set at p<0.05. SigmaStat version 2.03, Chicago, Ill. and the Minitab version 12.23, State College, Pa. statistical softwares were employed.

(58) Results

(59) Twenty-seven infants participated in the study and 222 measurements of distal EtCO.sub.2 and 212 of proximal EtCO.sub.2 were analyzed. In 10 infants proximal EtCO.sub.2 could not be measured continuously. Table 1 shows the characteristics of the patients who participated in the study.

(60) TABLE-US-00001 TABLE 1 Patients' characteristics (n = 27) Median Range Gestational age (weeks) 32.5 (24.8-40.8) Birth weight (g) 1835 (490-4790) Age of enrolment (days) 1 (1-26) Number of observations 8 (1-24) pH 7.34 6.5-7.5 FiO.sub.2* 0.31 0.21-1.00 PaO.sub.2/PAO.sub.2 ratio** 0.50 0.06-2.38 Oxygenation index (OI)*** 3.29 0.63-23.0 Primary diagnosis (n = 27 infants) Respiratory distress syndrome 19 Tracheo-esophageal fistula and esophageal atresia 3 Pneumonia 1 Primary pulmonary hypertension 1 Meconium aspiration syndrome 1 Hypoxic ischemic encephalopathy 1 Necrotizing enterocolitis 1 *FiO.sub.2 Inspired oxygen fraction; **PaO.sub.2/PAO.sub.2 alveolar/arterial oxygen tension ratio; ***OI = FiO.sub.2 mean airway pressure/PaO.sub.2

(61) The median (range) levels of PaCO.sub.2, dEtCO.sub.2, pEtCO.sub.2 were 46.3 (24.5-99.7) mmHg, 46.0 (20.0-98.0) mmHg, and 37.0 (12.0-71.0) mmHg, respectively.

(62) FIGS. 3A and B show the linear correlation between distal EtCO.sub.2, dEtCO.sub.2 (A) and proximal EtCO.sub.2, pEtCO.sub.2 (B) with arterial PCO.sub.2, according to some embodiments. While the correlation coefficient (r) of dEtCO.sub.2 and PaCO.sub.2 was adequate (r=0.72, p<0.001), the r of the pEtCO.sub.2 was poor (r=0.21, p=0.002).

(63) FIGS. 4A and B present the Bland-Altman plots of the differences between distal EtCO.sub.2, dEtCO.sub.2 (A) and proximal EtCO.sub.2, pEtCO.sub.2 (B) and arterial CO.sub.2, PaCO.sub.2, according to some embodiments. The mean difference (bias) and the standard deviation of the differences (precision) for the dEtCO.sub.2 were 1.58.7 mmHg , and for the pEtCO.sub.2 10.213.7 mmHg, respectively. The correlating medians (25 and 75 percentiles) were: 1.1 (5.6 and 2.7) and 10.3 (16.0 and 0.8), respectively. Although both, distal and proximal EtCO.sub.2 levels underestimated the PaCO.sub.2 level, dEtCO.sub.2 was more accurate than pEtCO.sub.2 as a non-invasive measure of PaCO.sub.2.

(64) dEtCO.sub.2 (21 samples) remained reliable as a measure of PaCO.sub.2, while pEtCO.sub.2 (19 samples) was distorted on the high range of PaCO.sub.2 levels (60 mmHg) (r=0.77, p<0.001 and r=0.21, p=0.38; biasprecision: 4.87.9 and 33.320.0; respectively).

(65) Table 2 shows the effect of the severity of pulmonary disease (assessed by PaO.sub.2/PAO.sub.2 ratio or by OI) on the accuracy of distal and proximal EtCO.sub.2 readings. It was found that dETCO.sub.2 still correlated with PaCO.sub.2, but its bias increased with the severity of pulmonary disease.

(66) TABLE-US-00002 TABLE 2 Relation between EtCO.sub.2 values and severity of lung disease Mild to Moderate Severe lung disease Mean (SD); r, p value Mean (SD); r, p value PaO.sub.2/PAO.sub.2 >0.3 (n = 168) 0.3 (n = 63) ratio P (Et-a distal) 0.24 7.3; 0.74, <0.001 4.2 10.5; 0.64, <0.001 CO.sub.2 P (Et-a proxi- 9.1 14.0; 0.07, =0.34 12.5 12.5; 0.35, <0.01 mal) CO.sub.2 Oxygenation <10 (n = 216) 10 (n 16) index P (Et-a distal) 0.7 8.2; 0.69, <0.001 9.0 8.1; 0.77, <0.001 CO.sub.2 P (Et-a proxi- 9.8 13.9; 0.13, =0.07 13.0 9.8; 0.52, =0.054 mal) CO.sub.2 All CO.sub.2 levels in mmHg

(67) The changes in PaCO.sub.2, and the simultaneous changes in proximal and distal EtCO.sub.2 were evaluated for consecutive measurements within each patient. The mean changes in PaCO.sub.2 were 0.129.3 mmHg and in dEtCO.sub.2 0.9010.8 mmHg, with r between the changes of 0.49, p<0.001. Mean change in pEtCO.sub.2 was 0.028.5 mmHg, with r of 0.17, p<0.05, compared to the simultaneous changes in PaCO.sub.2.

(68) This study shows that the novel method of measuring dEtCO2 through a double-lumen ETT had a better correlation and agreement with PaCO.sub.2 when compared to the standard mainstream pEtCO.sub.2 method in neonates. The accuracy of dEtCO.sub.2 decreased but it remained a reliable measure of PaCO.sub.2 even in the high range of PaCO.sub.2 (60 mmHg) or in conditions of severe lung disease.

(69) It was found that dEtCO.sub.2 was an accurate and reliable non-invasive method for estimating PaCO.sub.2. It had a good correlation with PaCO.sub.2 (n=222, r=0.72, p<0.001), which was slightly lower compared to mainstream pEtCO.sub.2 (n=411, r=0.83, p<0.001) as previously reported for NICU infants by Rozycki et at (10). The bias reported for dEtCO.sub.2 (1.58.7 mmHg) was even smaller than that reported by Rozycki et at for mainstream pEtCO.sub.2 (6.96.9 mmHg), and was well <5 mmHg, which is considered within the good agreement range (9, 10). In the study, the correlation and the agreement of dEtCO.sub.2 with PaCO.sub.2 were better than those for mainstream pEtCO.sub.2. Several investigators reported similar results for distal and proximal sidestream EtCO.sub.2 (17, 18) while others reported comparable accuracy of distal and proximal mainstream EtCO.sub.2 (11). However, neither of these studies measured dEtCO.sub.2 by a double lumen ETT, nor did they use the Microstream technique. The study results regarding the mainstream pEtCO.sub.2 should be interpreted with caution, as others reported better results for that method (10). This could result from different conditions in the different studies reflected by mixture of patients, severity of their lung disease, levels of leak around the ETT, and instrumentation used for measurements.

(70) Severity of disease was reported to affect the accuracy of capnometry in several studies. The more severe the ventilation perfusion mismatch, the higher the difference between EtCO.sub.2 and PaCO.sub.2 (9, 20). Parenchymal lung disease with ventilation perfusion mismatching is a common feature in NICUs. Sivan et at (20) reported that PaO.sub.2/PAO.sub.2 ratio >0.3 was associated with better agreement between EtCO.sub.2 and PaCO.sub.2 and Hagerty et at (9) found a higher gradient between EtCO.sub.2 and PaCO.sub.2 when comparing newborn with pulmonary disease and those receiving mechanical ventilation for non-pulmonary conditions. Different results were reported by other investigators. Tingay et at (19) found that the EtCO.sub.2 bias was independent of severity of lung disease and Rozycki et at (10) reported that measures of degree of lung disease (ventilation index and oxygenation index) had small influence on the degree of bias. In the study the agreement of dEtCO.sub.2 and PaCO.sub.2 decreased, but the bias in patients with PaO.sub.2/PAO.sub.2 ratio<0.3 remained <5 mmHg. It was assessed whether the level of PaCO.sub.2 affected the accuracy of EtCO.sub.2 readings, and found it to affect the pEtCO.sub.2 much more than the dEtCO.sub.2, which remained with adequate agreement with the PaCO.sub.2. Rosycki et at did not find that the accuracy of pEtCO.sub.2 was affected by the PaCO.sub.2 level (10). The findings suggest that dEtCO.sub.2 as evaluated in the study could be used as a reliable non-invasive method for PaCO.sub.2 assessment in the full spectrum of NICU patients.

(71) Although the Microstream sidestream capnography was used previously in (only) two studies in newborns (9, 19), this is the first time a double lumen ETT is used for the disclosed perpose, which allowed continuous measurement of dEtCO.sub.2 via its extra lumen.

(72) The intention of the Microstream technique is to improve the accuracy of sidestream capnomtery which is traditionally considered less accurate than the mainstream capnometry (11, 13, 14, 15, 16). Microstream capnography employs a sampling flow rate of 50 ml/min, approximately one third of that used by previous studies with conventional sidestream systems. This low flow rate eliminates the competition for tidal volume and also decreases condensation within the system. Because of the highly CO.sub.2specific infrared source (emission that exactly matches the absorption spectrum of the CO.sub.2 molecule), the sample cell utilizes a much smaller volume (15 l) that permits a low flow rate without compromising response rate or accuracy. These features preserve accuracy by preventing mixing of the small inspiratory and expiratory volumes observed in newborns, while rapid response time is maintained by laminar gas flow throughout the breathing circuit (22). The new low-flow sidestream capnograph (Oridion Medical Inc., Needham, Mass., USA) was tested when connected to the side port of the proximal ETT by Hagerty et at (9), and they reported a gradient of 3.42.4 mmHg in ventilated infant without pulmonary disease and 7.43.3 in those with pulmonary disease. Tingay et at (19) also used the Microstream technique (Agilent Microstream system, Andover, Mass., USA) for monitoring pEtCO.sub.2 in infants during neonatal transport. They reported that the pEtCO.sub.2 had a linear relation with PaCO.sub.2 but had an unacceptable underestimation of PaCO.sub.2 (8.25.2 mmHg), and did not trend reliably over time within an individual patient. In the study, using the Microstream technique (Oridion Medical Inc., Needham, Mass., USA), but measuring dEtCO.sub.2 via the side port of the double lumen ETT, the agreement with PaCO.sub.2 improved, in infants with both mild and severe pulmonary disease (0.247.3, and 4.210.5; respectively). The improvement could be related to distal measurements of EtCO.sub.2. This technique which measures EtCO.sub.2 close to the carina, may be less affected by the ventilatory circuit flow and leaks around the uncuffed ETTs used in neonates and thus better represent the accurate PaCO.sub.2. dEtCO.sub.2 as opposed to pEtCO.sub.2 are not affected by flow sensors which are commonly used nowadays with the new ventilators (flow sensors in the study prevented the use of pEtCO.sub.2 in few infants because of inadequate continuous measurements).

(73) The novel method of measuring dEtCO.sub.2 via a double-lumen endotracheal tube was found to have good correlation and agreement with PaCO.sub.2, and is thus a reliable in conditions of severe lung disease. dEtCO.sub.2 was more accurate than the standard mainstream pEtCO.sub.2 method as assessed in the study. EtCO.sub.2 does not replace PaCO.sub.2, but may be useful for trending and for real time continuous screening of abnormal PaCO.sub.2 levels. As noninvasive CO.sub.2 monitoring may be of importance for the short and long term outcome of intubated neonates, and as the current available methods are limited, medical teams should consider the use of this non-invasive method of assessing PaCO.sub.2 in NICUs.

Example 2

Correlation between Sampling through a Double Lumen ETT and Blood Gas in Patients Ventilated by HFV

(74) Eight patients ventilated by HFV were tested, comparing mainstream capnography to Microstream capnography wherein the sampling line is connected to the distal end of a double lumen ETT. In most of the cases 2.5 mm ETT (internal diameter of the main endotracheal tube) were used. Correlation to blood gas was used as the reference.

(75) Continuous distal sampling with minor liquid issues was conducted (without having to toggle). Further, two Nafion pieces were placed along the sampling line, one next to the double lumen connector, and one about 40 cm down the line. The second Nafion was used since often the neonate is in a controlled humidified incubator, and hence one Nafion must be placed also in the outside environment. The results are described in FIG. 5 which shows the linear correlation between distal EtCO.sub.2, dEtCO.sub.2 and arterial CO.sub.2, PaCO.sub.2 in patients ventilated with High Frequency Ventilation (HFV), according to some embodiments. The correlation between dEtCO.sub.2 and PaCO.sub.2 was shown to be much better than the correlation between pEtCO.sub.2 and PaCO.sub.2.

(76) In the description and claims of the application, each of the words comprise include and have, and forms thereof, are not necessarily limited to members in a list with which the words may be associated.

(77) The invention has been described using various detailed descriptions of embodiments thereof that are provided by way of example and are not intended to limit the scope of the invention. The described embodiments may comprise different features, not all of which are required in all embodiments of the invention. Some embodiments of the invention utilize only some of the features or possible combinations of the features. Variations of embodiments of the invention that are described and embodiments of the invention comprising different combinations of features noted in the described embodiments will occur to persons with skill in the art. It is intended that the scope of the invention be limited only by the claims and that the claims be interpreted to include all such variations and combinations.

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