Patent Grant
11464934
The present invention relates to a device, method and system for delivering CO2 into an inspiratory gas stream to formulate a blended respiratory gas in a manner that continuously maintains a target CO2 concentration in a volume of the inspired respiratory gas, for example, over the course of a breath or a volumetrically definable part thereof or a series of partial or full breaths.
The arterial partial pressure of CO2(PaCO2) is intimately related to the acid base status of the blood. CO2 combines with water to form carbonic acid. The higher the PaCO2 the more acid is the blood. CO2 is formed in the body by metabolism and is eliminated from the lungs by ventilation. The relationship between PCO2 and ventilation is a rectangular hyperbola with PCO2 becoming infinite at low ventilations and reaching an asymptote of 0 at infinite ventilation. Ventilation is therefore controlled in response to chemosensitive neurons located in the brainstem and surrounding major arteries.
There are many occasions where it is required to induce a change in PaCO2 in a subject or patient. One example is to study the responses of various body systems to changes in CO2 such as the chemoreceptor cells themselves, breathing pattern, arousal, brain blood flow, coronary artery blood flow, ocular blood flow, renal blood flow, changes in blood vessel diameter in various organs and major arteries such as the brachial artery, and changes in brain waves, behavior and seizure threshold. We pick brain blood flow, blood volume and oxygen extraction fraction as an example for the use of changes in PaCO2. For example brain blood flow can be measured by various modalities that include trans-cranial Doppler, positron emission tomography (PET) and single proton emission tomography (SPECT), and nuclear magnetic resonance imaging (MRI) techniques such as blood oxygen level dependent (BOLD) and arterial spin labeling (ASL) echo. CO2 is used as the provocative stimulus to induce a change in blood flow and thus measure the vascular reactivity. Traditional methods have assumed that infusing CO2 into a mask will change the PaCO2. Infusing the CO2 into the mask changes the exhaled PCO2 but this is unreliably related to the PaCO2, the actual physiological stimulus at the site of action. It has been shown by Prisman et al1. and Hoskins et al.2 that this is totally ineffective (see discussion in Prisman1 and Mark et al.3, 4). Still, infusion of CO2 into a mask or fixing the inspired PCO2 is nevertheless still used for studying brain vascular reactivity. With this method, one can detect a change in brain blood flow but because one doesn't know the PaCO2, the actual reactivity is unknown. For example, a small change in the measure of blood flow may be due to low reactivity or small change in PaCO2.
An improved method of implementing changes in PaCO2 has been presented by Prisman et al.1. The theory presented by Slessarev et al.5 is that sequential gas delivery provides good reliability in targeting a change in PaCO2. The theory of such targeting requires the delivery of a first gas which has a predetermined concentration of oxygen and CO2 to affect a PaCO2 at the first part of the breath and the remainder of the breath consists of a second gas which has CO2 concentration equal to the target PaCO2. Ito et al.6 applied such a circuit to spontaneously breathing humans and found that targeting with this system the expired partial pressure of CO2 was substantially equal to PaCO2 within about 2 mmHg. This is sufficiently accurate for most, but not all purposes. For example, calibration of MRI BOLD signals to measure oxygen consumption of the brain require as accurate determination of PaCO2 as can be obtained, and small discrepancies reduce the value of the calibration (Mark et al.). One source of error with the sequential gas delivery circuit is that some first gas continues to flow and be inhaled during the second gas delivery phase where it is desired that only second gas be inhaled. This is a limitation of all sequential gas delivery circuits. A variety of active or passive valves to prevent the first gas delivery during the phase where only second gas delivery is desired make the system more cumbersome, uncomfortable for the subject, and more expensive.
According to one aspect, the present invention is directed to a method of preparing a carbon dioxide (CO2)-containing gas (Gn) that is organized for delivery in tandem with a second gas (G0), in manner that composes a respiratory gas (GR) and maintains a target CO2 concentration (FCO2T) in a cumulative volume of the GR of interest (CVGRI), the method comprising:
for each successive time point of interest in a growing time period comprising all time points of current interest T1 to Tlast, each successive time point in turn a Tlast:
As of each successive time point of interest Tlast (for convenience also called Tcurrent), in a time period of interest, the CVGR is understood to comprise all incremental volumes of G0 organized for delivery as of Tlast (which cumulatively make up, as of each successive Tlast, a new CVG0 for the respective incremented time period of last interest comprising the time pointsT1, to last Tlast) and all incremental volumes of Gn organized for delivery as of Tlast (which cumulatively make up, as of each successive Tlast, a new CVGn for the respective incremented time period of last interest comprising the time pointsT1 to last Tlast). As described below, consonant with one suitable placement of the sensors used to track the actual incremental volumes of gas organized for delivery, input of CVGR for the last incremented time period may be simply obtained by adding the respective CVGn and CVG0 values for this time period (sensor placement is organized to track incremental volumes of G0 and Gn as of each Tlast which are then incremented to obtain new values of CVGn and CVG0 for each successive time point). Alternatively, input of the CVGR may be obtained by using a sensor to directly track incremental volumes of GR organized for delivery. As explained below, tracking respective CVGn and CVG0 values for each Tlast may in some instances be sufficient to compute a respective incremental volume of Gn that must be delivered as of Tlast so that the cumulative volume of CO2 in the CVGR equals FCO2T (e.g. without directly computing a respective CVCO2 value for each time point of interest). Various embodiments of the invention described hereafter refer to obtaining input of alternative cumulative volume terms needed for computing a respective incremental volume of Gn that must be delivered so that the cumulative volume of CO2 in the CVGR equals FCO2T.
The expression “of interest” with reference to time points of interest, is to be understood to encompass time points that simply correspond to events that mark the beginning or end of a period of gas delivery (e.g. for a certain number of breaths, planned or arbitrarily terminated, or completion of a treatment or completion of a contemporaneous medical procedure or diagnostic test) but could also mean “directly” of interest insofar as the time span of making GR available for breathing begins and ends at specified points in time, whether predetermined or simply arbitrary. It will be appreciated that computation of an error signal and related control of a gas delivery device is done at selected time increments (e.g. every “x” milliseconds) which implies, that within a time span of interest, time points corresponding to those increments are inherently of interest. Since time points of interest are generally time points used to compute en, contiguous time points of interest are considered to be adjacent time points defining intervals of interest for computation of en. Similarly, a volume or cumulative volume of interest may be of interest simply in the sense that it defines one or a series of successive cumulated volumes that define reference volumes for calculation of an error signal.
By computing and controlling the delivery of an incremental corrective volume of Gn that must be added to combined volume of the CVGn and CVG0 (the CVGR) to target the FCO2T as of each successive time point Tlast, the Gn is understood to be functionally organized for delivery in tandem with the G0.
In one preferred embodiment of the invention, each incremental volume of gas organized for delivery by a gas delivery means (GDn) may be flowed to a patient, for example via an output port which leads unimpededly to a patient airway interface (e.g a mask) or a volume of gas that a patient is free or forced to intake (closely following release by the GDn). In this connection, it is convenient to speak of incremental volumes, of defined magnitude determined by a sensor, ‘delivered’ (i.e. released for delivery) by a GDn (as well as incremented cumulative gas volumes based on these incremental volume values), as ‘delivered’ volumes. The phraseology ‘actually delivered’ may be also be used (with the same intended meaning) for emphasis.
The term “blending” may be used to describe the act of organizing delivery of Gn in tandem with the G0 and hence the term blending optionally encompasses physical blending and coordinated release of components of the GR to a patient.
According to another aspect, the present invention is directed to a method of using a respiratory gas delivery system having one or more gas output ports to coordinate the output of a carbon dioxide (CO2)-containing gas (Gn) and a second gas (G0), in a manner that composes a respiratory gas GR, the method comprising:
for respective time points in a series of time points of interest:
The term “equals” as used herein preferably connotes mathematical equality but more broadly connotes a functional approximation of FCO2T based on computation of a corrective volume of CO2 in circumstances where such computation relies on inputs of incremented cumulative volumes G0 and/or GR and Gn and/or CO2 i.e. such data is used as a basis upon which to compute, at respective time points of interest, a volumetric correction factor used to deliver an incremental amount of Gn to adjust the cumulative amount of Gn in a cumulative volume of GR of interest so that the cumulative amount of CO2 is adjusted to at least functionally achieve a FCO2T. The term “target” in the same vein, broadly connotes the use any suitable control signal that implement the computation in step c) to deliver a corrective incremental volume of Gn.
The phrase “obtaining input” is meant to be broadly construed as encompassing any form of obtaining input that allows the input to be used. For example, a processor, optionally, in the form a microprocessor, may be programmed to receive a signal or data, for example a signal generated by a sensor or user input, or perform a computation using, for example, the aforementioned input, in order to generate the particular inputs required to compute an error signal, and ultimately, a control signal to a gas delivery device GDn.
Optionally, CVGRI is equated to CVGR. Optionally, CVGRI consists of (is equated to) or comprises the CVGR for example the sum of CVGR, and an incremental volume of GR that is designated to be delivered based on an adding a corrective incremental amount of Gn to an incremental volume of G0 predicted to be delivered to an output port in an ensuing time point for which sensor data is not available (optionally relying on actual data for relevant time points, optionally one more or more immediately preceding time points). The CVGRI may consist of, comprise or otherwise takes into account the CVGR (as a base principle, taking CVGR into account enables computation of a corrective volume of Gn based on volumes of gases actually made available for delivery). Therefore, CVGRI is preferably a selected function of CVGR, optionally a function which adds one or more defined incremental volumes to the CVGR as exemplified herein. The invention also contemplates a function in which a defined volume is subtracted from CVGR, for example as another form of corrective measure, for example for adjusting the inspired “dose” of carbon dioxide.
Optionally, a CVGR is available for immediate inspiration (i.e. following commencement of Gn delivery by GDn to an output port) and FCO2T is attained within a cumulative GR inspiratory volume of no greater than 50 litres, optionally no greater than 10 litres, optionally no greater than 5 litres, optionally no greater than one liter optionally no greater than 500 ml, optionally within a cumulative GR inspiratory volume of no greater than 100 ml, optionally within a cumulative GR inspiratory volume of no greater than an average human adult or infant breath, optionally within a cumulative GR inspiratory volume of 25 mls, optionally within a time span of a single average inspiration, optionally within in a time span of 1 to 3 seconds. Optionally, the FCO2T is continuously maintained after being after being attained.
The phrase “in tandem” means at least coordination in a volumetric sense to achieve proportioned output of Gn that matches output of G0. However, the output of the respective components of a respiratory gas GR in a respiratory gas delivery system may typically be needed or potentially needed in an immediate sense (in real time), for example, where the output flows in real time to a patient airway interface such as a mask or endotracheal tube or to one more gas reservoirs the contents of which may (either immediately, imminently or as needed) be drawn on or delivered breath by breath. The present invention notably enables such coordination to be scaled from both a time and volumetric standpoint to at least within a human (adult or infant) breath so that the volume of pure CO2 in the CVGRI (where CVGRI is a breath or a partial breath of minimum size e.g. 10-25 ml., having regard to the volume/precision specifications of the GDn and other components) equals FCO2T.
The term output port with reference to delivery of Gn broadly means any port or junction downstream of a gas delivery means (GDn), through which the volumetric output of Gn is controlled as described below so that actual respective volumes of Gn delivered downstream of the GDn target FCO2T. Because incremented amounts of G0 are directly or indirectly part of the input of a control system, optionally embodied in a computer, the incremental amounts Gn for respective time points are effectively delivered in tandem with delivery of the G0 (delivery may result in release of G0 to a patient in real time or optionally take the form of volumetrically controlled accumulation of the G0 e.g. if a combined gas or respective individual gases are accumulated for delivery). As described below the invention contemplates the use of a control system to set a target FCO2T, to obtain inputs of the requisite cumulative volumes of G0 (CVG0) or GR (CVGR) over a period comprising the series of time points of interest, to obtain input of a cumulative volume of Gn (CVGn) or CO2 (CVCO2) over a period comprising the series of time points of interest, to compute an corrective amount incremental amount of Gn needed to target FCO2T (en) for those respective time points, to control the gas delivery means (e.g. a valve) in order to increment the delivered amount of Gn so as to target FCO2T and where required (e.g.) where the concentration of CO2 in the Gn and optionally G0 is not fixed to receive input of sensors that detect concentration of gases and compute an en accordingly. As described below this control system may be variously embodied in one or more hardware components in a manner well known in the art.
According to one embodiment of the invention, a respiratory gas delivery system may comprise a conventional ventilator, anesthetic machine or other respiratory gas delivery device (machine or manually operated) having an output port for the G0 (leading, optionally unimpeded, to a G0 containing reservoir or a patient airway interface) which is operatively coupled to a separate Gn delivery device having an output port directly into the G0 (for example into a G0 delivery conduit) or into a common volume (e.g. a patient airway interface, reservoir, manifold, connector) or different volumes which are organized to be delivered proportionately for maintaining FCO2T and preferably contemporaneously and in real time (i.e. resulting in the targeted concentration of CO2 in a volume of the GR to be maintained (after an initial ramp up time) continuously. The cooperation among two devices having respective individual output ports or a common output port from the standpoint of eventual output to the patient may be understood to be a retrofit or of a priori design, The invention also contemplates a respiratory gas delivery system in the which a G0 delivery system and Gn delivery system are integrated in a common unit.
Optionally, as described below, at successive time points within a series of time points of interest, an error term as hereafter described, may be computed.
As elaborated below, a key nature of the respective time points of interest are those for which there are available inputs of incremented cumulative volumes G0 and/or GR and Gn and/or CO2. These inputs may be derived from sensors that generate the signals required to obtain input of the incremented cumulative volumes of gases delivered to an output port. In this manner the requisite input is obtained for computing, at respective time points, an incremental volume of Gn that must be delivered to an output port in tandem with the delivered G0 so that the cumulative volume of CO2 in the CVGRI equals FCO2T. Accordingly, the series of time points of interest for which respective cumulative volumes of gases are obtained and computations of an error term, as described below, are made, are understood to minimally accord at least with a particular application for which the respiratory gas delivery system is used i.e. requisite degree of precision for proportionally matching Gn and G0 at least volumetrically and to match the requisite contemporaneous nature of the coordination in terms of ensuring the fraction and/or size and/or number of the breath(s) for which a CO2 adjusted composition of a CVGRI is sought to be achieved is timely attained and maintained. Accordingly, the respective time points of interest for which respective incremented volumetric inputs (CVG0 and/or CVGR and CVGn and/or CVCO2) to compute an error term is obtained, must at least closely correspond to one another and to the time points for which sensor data input is obtained.
Optionally, as described below, at successive time points within a series of time points of interest an error term may be computed. Optionally, this series of time points of interest may be described as the most current continuous period of interest for which the targeted CO2 concentration in a cumulative volume of GR of interest is maintained. The invention contemplates that the actual delivery of this CVGRI to the patient may lag in time. Therefore, Tcurrent is not necessarily a Tnow in the sense of according with a current device clock time/volume sensor reading. Nevertheless, each successive time point is preferably a time point of interest at least in the sense in which it corresponds to one of the respective time points for which incremented cumulative volumes required for computation of en is used. Each respective time point in a series of interest can be understood to become, in turn, a current time point Tcurrent (optionally a Tnow) at which the delivered volumes of Gn, G0, and CO2 are updated based on sensor readings and these updated values can be used at each respective time point of interest for computing an error term en. The error term en is optionally equated to a volume of Gn that must be delivered so that the volume of pure CO2 in the combined volumes of CVGn, CVG0, and en equals FCO2T. The error term is converted by a controller (VCn) into a signal that is delivered to a GDn so that an incremental volume of Gn is delivered by the GDn to target a CO2-concentration of FCO2T in the incremented volumes of CVGn and CVG0. Optionally, the VCn takes the form of a PI controller. Optionally, the VCn takes the form of any controller known to those skilled in the art that can accept input of en and compute a signal for GDn to deliver an incremental volume of Gn to target FCO2T. The output to the GDn for a respective Tcurrent may be generated from a weighted sum of en for the respective Tnow, the integral of en over a time period T1 . . . Tcurrent, and the derivative of en for the respective Tcurrent.
According to another aspect, the present invention is directed to a device for coordinating the output of a carbon dioxide (CO2)-containing gas (Gn) and a second gas (G0), in a manner that composes a respiratory gas GR, the device comprising:
The present invention is directed to a method of delivering to a subject a carbon dioxide (CO2)-containing gas (Gn) and a second gas (G0), in a manner that composes a respiratory gas GR, the method comprising:
for respective time points in a series of time points of interest:
The present invention is also directed to a method of blending a carbon dioxide (CO2)-containing gas (Gn) and a second gas (G0), in a manner that composes a respiratory gas GR for delivery to a subject, the method comprising:
for respective time points in a series of time points of interest:
In another aspect, the present invention is also directed to an integrated circuit (IC) chip configured for carrying out a method as described herein.
In another aspect, the present invention is also directed to a computer program product comprising a non-transitory computer readable medium encoded with program code for controlling operation of an electronic device, the program code including code for computing an error term en corresponding to the incremental volume of Gn computed for the respective time points of interest. Optionally, the program code includes code for computing or obtaining input of a set of parameters comprising CVGR and CVCO2. Optionally, the program code includes code for controlling a gas delivery means (GDn) so that respective delivered incremental volumes of Gn target FCO2T.
In another aspect, the present invention is also directed to device comprising an integrated circuit chip configured for carrying out the method, for example a printed circuit board (comprising discrete electronic components). The device optionally includes at least one gas delivery means and optionally at least one volume sensor as hereinafter defined. The device optionally includes an input device for inputting FCO2T. Optionally, FCO2T can be input via a variety of means including, but not limited to, a keyboard, mouse, dial, knob, touch screen, button, or set of buttons. Optionally, the target FCO2T can be changed at any time.
The device optionally includes at least one CO2 containing gas delivery conduit.
In one embodiment, the present invention is directed to a method for adding at least one carbon dioxide-containing gas (Gn) to an inspiratory gas (G0), to formulate a respiratory gas (GR) for delivery to a subject, and to maintain a targeted concentration of carbon dioxide (FCO2T) in a volume of the GR of interest (CVGRI), comprising:
for each of a group of respective time points of interest comprising
T1 . . . Tcurrent, each in turn a respectiveTcurrent:
In one embodiment, an error term (en) is computed that represents the incremental volume of Gn that must be delivered to the subject so that the cumulative volume of CO2 in the CVGRI (e.g. the actual CVGR) equals FCO2T.
Therefore, according to one embodiment, the invention is directed to a method of adding at least one carbon dioxide (CO2) containing gas (Gn) to an inspiratory gas G0, to formulate a respiratory gas (GR) for delivery to a subject, and to maintain a targeted concentration of CO2 in a volume of the GR, comprising:
for each of a group of respective time points of interest T1 . . . Tcurrent each in turn a respectiveTcurrent:
In one embodiment, a suitable controller (e.g. a PI or PID controller) is used to control the gas delivery means (GDn) so that the delivered incremental volume of Gn targets FCO2T.
The term “fraction” and “concentration” are generally used interchangeably herein based on the understanding that a particular choice of algorithm and units (if any) for expressing concentration may vary based on whether partial pressures, fractional concentrations or percentages are used for expressing a target concentration of CO2 in a volume of GR. The abbreviations FCO2T and CO2T are also used interchangeably.
The term “respiratory gas” means a group of at two component gases that are suitable for inhalation by a subject individually or at least when combined and that meet a criterion with respect the concentration of carbon dioxide in any combined volume of the group of component gases. Accordingly, in a clinical setting where any particular combined volume of the component gases is inhaled over a particular time period by a subject, as a single stream of combined component gases or multiple streams in parallel, the FCO2T with respect to a cumulative volume of GR inhaled by the subject over a period of interest (e.g. a single breath) will have been maintained.
The actual cumulative volume of GR (referred to as CVGR) is understood to include, as preferred, the incremental volume of Gn that must be delivered to the subject so that the cumulative volume of CO2 in the CVGRI equals FCO2T.
As described above, in one embodiment of the invention the CVGRI is equated to the CVGR. In one embodiment of the invention described below, at a respective Tcurrent, an assumption is made about how much inspiratory gas G0 (the G0 is alternately referred to as a second gas, the Gn alternately being referred to as a first gas) will be delivered between Tcurrent and an ensuing time point. Accordingly, in addition to computing the incremental volume of Gn that must be delivered so that the cumulative volume of CO2 in the CVGR equals FCO2T it may expedient to compute at Tcurrent, the Gn that would be need to be delivered to target the FCO2T within a particular assumed incremental amount of G0.
In the latter connection, CVGRI may optionally be computed as the sum of the CVGR, the assumed incremental volume of G0 and the incremental volume of Gn that would be sought to be delivered to target the FCO2T within that incremental amount of G0. The computation of CVGRI may serve other purposes as well and hence computation of CVGRI (however approached) is understood to preferably be a function of an actual CVGR value, for a respective Tcurrent, whereby one can consequently compute the incremental volume of Gn that must be delivered so that the cumulative volume of CO2 in a particular cumulative volume of GR (i.e. taking into account a CVGR value) equals FCO2T.
Obtaining input of CVGn is expressed as an alternative to obtaining input of CVCO2. In most cases, using CVCO2 as an input for computation of en will be preferable (optionally as an incremented volume of CO2, incremented at each successive Tcurrent within a series of time points of interest) as this approach best serves (in the broadest range of circumstances) the computational purpose of continuously tracking the incremental volume of pure CO2 that must be delivered to target FCO2T having regard to the incremented cumulative volume of pure CO2 contributing to the incremented cumulative volume of GR. Obtaining input of CVGn incidental to the goal of computing the error term en may be understood to be practical as an input parameter, in a physical sense (from volume sensor readings), and beyond that tracking CVGn computationally may in theory be adequate (e.g where the G0 is devoid of CO2 and the concentration of CO2 in Gn is fixed) as a surrogate method of tracking CVCO2. However, in most instances, using CVGn as a plausible alternative input parameter for computing the error term en (e.g. especially where it must be matched with a changing value of a variable concentration of CO2 in Gn—and optionally also a fixed or changing value of a variable concentration of CO2 in G0—applicable to each respective Tcurrent) may be computationally unwieldy. Therefore, optionally, determining a cumulative volume of pure CO2 (CVCO2) delivered in a particular time interval, for example, a period of interest T1-Tcurrent, may serve the purpose of computing en most universally and efficiently by accommodating input of a value for the concentration of CO2 in Gn (this value may 100% or less than 100%) and a value for the concentration of CO2 in G0 (as this value may be 0% or more than 0%). This may be done by incrementing the volume of CO2 from the last Tcurrent by the incremental volume of G0 and Gn delivered since the last Tcurrent weighted by their concentrations of CO2. Therefore it will be appreciated that even though obtaining input of both CVCO2 and CVGR for each respective time of interest is the most universally pragmatic way of computing the corrective volume of Gn that must be added to the cumulative volume of GR as of each time point of interest, in some instances, as explained above, the input sufficient to compute this corrective volume may be geared to alternative mathematically equivalent terms and algorithms. Hence, it will be appreciated that certain alternative combinations of inputs are to be viewed as particular embodiments falling within a broader range of alternatives, namely inputs sufficient to compute CVCO2 and CVGR (i.e. algorithms using surrogate cumulative volume terms and any other input values such as CO2 concentrations in Gn and G0 would invariably use a combination of inputs sufficient to compute both CVCO2 (a cumulative volume of the pure component of interest) and CVGR)
As elaborated below, each successive time point within a period of interest becomes a current time point Tcurrent at which the cumulative volumes of pure CO2 and/or Gn and, G0 and/or GR, are updated based on sensor readings (which may output actual incremental volumes of the respective gases at each respective Tcurrent) and these updated values can be used for computing the error term en. The error term is a volume of Gn computed at successive time points Tcurrent that is converted by a controller into a signal delivered to the GDn to target (having regard to the limitations of the hardware) the desired concentration of carbon dioxide that is input or preset (CO2T). Thus the GDn is signaled to deliver a corrective volume of gas. Expressed in terms of time points identified herein, the corrective volume may optionally be considered to be delivered during the time interval beginning at the respective Tcurrent and optionally ending at Tcurrent+, optionally the immediately next ensuing Tcurrent+1. The term “gas delivery means”, abbreviated GDn and alternatively to as a “gas delivery device” refers to specifically to hardware for delivering (e.g. releasing, where the source gas is under pressure) specific volumes of Gn into the respiratory gas inspired by the patient, preferably a device that is adapted to introduce volumes of variable incremental size into the respiratory gas, for example directly into a Gn carrying conduit, optionally into an inert conduit (inert vis-à-vis the composition of the Gn), optionally a conduit that feeds directly into a conduit carrying the G0 stream such as an inspiratory limb of a breathing circuit. The gas delivery means may be any known gas delivery device such as a gas injector, or a valve, for example, a proportional flow control valve.
The term “pure CO2” is used broadly to facilitate defining a fraction of a volume of delivered CO2 containing gas (theoretically pure CO2) that allows one to compute en and/or other parameters described herein
Optionally, in one embodiment of the invention, the output to the GDn for a respective Tcurrent is generated from a weighted sum of en for the respective Tcurrent and the integral of en for the respective Tcurrent (e.g. based on a signal from a PI controller). Optionally, the gas delivery means GDn is controlled using a controller (VCn) in the form of a PID controller. Optionally, the group of respective time points of interest defined with respect to the respective Tcurrent define a cumulative time period (Tvariable) beginning at a resetable Tstart and ending at an incrementally advancing time point (Tend) equated to the respective Tcurrent and the signal to the GDn applicable to a respective Tcurrent is computed using only an actual CVGn and/or CVCO2, and CVG0 and/or CVGR delivered in the time period Tvariable. In another embodiment of the method, the group of respective time points of interest defined with respect to the respective Tcurrent define a cumulative time period (Tvariable) beginning at a resetable Tstart and ending at a an incrementally advancing time point (Tend) equated to the respective Tcurrent and the signal to the GDn for a Tvariable corresponding to a respective Tcurrent is computed based on:
A variety of different strategies could be used to add a predictive element to the aforementioned approach of keeping the delivered Gn in step with the amounts of G0 delivered so that the en is lessened or less variable. According to one embodiment herein, the signal delivered to the GDn is computed based on the sum of the output of the controller VCn and a volume of Gn that must be added to G0P (GnP) so that the incremental volume of CO2 in the combined volume of G0P and GnP equals FCO2T. A variety of alternative methods could be used to compute G0P and FCO20P. Optionally, G0P for the time interval ΔT corresponding to a respective Tcurrent is equated with a pre-defined value, an incremental volume of G0 delivered during a previous time interval of interest, or with an average or weighted average of the volumes of G0 delivered in a plurality of previous time intervals of interest. Optionally, FCO20P can be equated with a pre-defined value, a concentration of CO2 in the G0 at a previous time point of interest, or with an average or weighted average of the concentration of CO2 in the G0 at a plurality of previous time points of interest. In general, G0P and FCO20P can be computed based on any combination of past data including, but not limited to, incremental volumes of G0 delivered or the concentration of CO2 in G0, and/or the rate of change of G0 delivery or the rate of change of the concentration of CO2 in G0, at one or a plurality of time points or time intervals of interest. Methods for computing G0P and FCO20P based on past data include, but are not limited to, averages, weighted averages, artificial intelligence, pattern recognition, rule definitions, look-up-tables, empirical formulas, or heuristics.
Optionally, the Tvariable corresponding to a respective Tcurrent is selectable based on a volumetric dimension of CVG0 or CVGR of interest, or a volumetric dimension of CVCO2 or CVGn of interest, a set of time points defined by an external event or a set of time points corresponding to a part of an inspiratory cycle, a full inspiratory cycle or a series of, parts of or full, inspiratory cycles. For example, the device of the present invention may be used to simulate sequential delivery of a pre-defined volume of G0 delivered in the first part of any inspiratory cycle and a gas having a CO2 content approximating the subject's arterial PCO2 for the remainder of any inspiratory cycle.
As described above, in one embodiment, the GDn is a proportional flow control valve. The invention also encompasses intermittently turning on and off a two way solenoid, etc.
Optionally, the cumulative volume of Gn (CVGn) actually delivered at respective points T1 . . . Tcurrent is obtained via a “volume sensor” (VSn) which can be constituted by any hardware for directly or indirectly measure a volume of Gn e.g. an incremental volume of Gn, for example, a spirometer, a flow meter (by computing the integral of the flow), a CO2 analyzer which can be used, for example, to deduce the flow of Gn which is then integrated to arrive at a volume etc. Input of a cumulative volume of G0 (CVG0) or GR (CVGR) actually delivered over all time points T1 . . . Tcurrent may can be implemented by employing the output a second volume sensing means (a VS0 or VSR) depending on whether the volume of G0 (VS0) or the total volume of respiratory gas (VSR) is being measured and/or computed.
The term “ascertained” when referring to a concentration of CO2 in Gn or G0 applicable to any respective Tcurrent (or in an analogous context) is used to broadly refer to a variety of instances e.g. where a value is determined for a respective Tcurrent by a gas analyzer; where the need for ascertaining the CO2 concentration is obviated by the algorithm (e.g. the fractional concentration of CO2 is not directly taken into account as an input, for example, where the device is particularly to adapted to a Gn consisting entirely of CO2 or G0 with 0% CO2); where the concentration of CO2 in the added gas is a fixed value based on a known concentration of CO2 in the CO2 containing source gas Gn (e.g. an inputable preset concentration such as 90% or 100% CO2) or where the concentration of CO2 in the G0 is a fixed value based on a known concentration of CO2 in the G0 (e.g. 0% CO2 in air).
Optionally, the function of the controller VCn is carried out by a microcontroller which optionally also receives and/or computes the various inputs described above including one or more of the following: for each of a group of respective time points of interest T1 . . . Tcurrent: FCO2T, CVGn, CVG0 and/or CVGR, an error signal (en) equal to the volume of Gn that must be delivered to the subject with the G0 so that the cumulative volume of CO2 in CVGR equals a desired fraction FCO2T; the output(s) of a volume sensing means (VSn and/or VS0 and/or VSR) and optionally, the output of a gas analyzer. Optionally, the inputs and computations are carried out by a general purpose microprocessor or CPU.
In one aspect, the invention is directed to a computer program product comprising a computer readable medium (non-transitory) encoded with program code for controlling operation of a device, the program code including program code for obtaining input of or computing, for each of a group of respective time points of interest T1 . . . Tcurrent, each in turn a respectiveTcurrent, a set of parameters for computing an error signal (en) equal to an incremental volume of a CO2 containing Gn that must be delivered in step with a G0 so that the cumulative volume of CO2 in CVGR is maintained at a desired fraction FCO2T. In one embodiment, the set of parameter includes a respective CVCO2 and CVGR for each respective Tcurrent. In one embodiment, the program code comprises program code for controlling a gas delivery means (GDn). In one embodiment, the program code generates a suitable signal corresponding to an actual incremental volume of CO2 needed to targets FCO2T for each respective Tcurrent within the group of respective time points of interest T1 . . . Tcurrent. Any suitable method of control known to those skilled in the art, for example, a form of PI or PID control may be included in the program code.
It is understood that any input, computation, output, etc described herein can be accomplished by a variety of signal processing means including, but not limited to, a programmable processor, a programmable microcontroller, a dedicated integrated circuit, a programmable integrated circuit, discrete analog or digital circuitry, mechanical components, optical components, or electrical components. For example, the signal processing steps needed for executing the inputs, computations and outputs can physically embodied in a field programmable gate array or an application specific integrated circuit.
In another one aspect, the present invention is directed to a control system for a respiratory gas delivery system that controls the coordinated output of a carbon dioxide (CO2)-containing gas (Gn) and a second gas (G0), in a manner that composes a respiratory gas GR, the control system comprising:
for respective time points in a series of time points of interest:
Optionally, the control system includes means to obtain input of a FCO2T It is understood that the control system is used to deliver the respective components of the GR in a manner that enables the requisite volumes to be tracked, whether the delivery is to an area of common volume or separate volumes organized to be delivered coordinately. Optionally, the control system is embodied in a computer as broadly defined herein.
In one aspect, the present invention is directed to a computer readable memory having recorded thereon computer executable instructions for carrying out one or more embodiments of the above-identified method. The invention is not limited by a particular physical memory format on which such instructions are recorded for access by a computer. Non-volatile memory exists in a number of physical forms including non-erasable and erasable types. Hard drives, DVDs/CDs and various types of flash memory may be mentioned. The invention, in one broad aspect, is directed to a non-transitory computer readable medium comprising computer executable instructions for carrying out one or more embodiments of the above-identified method.
In one embodiment, the invention is directed to IC chip designed to implement a method according to the invention. In one embodiment, the invention is directed to a printed circuits board comprising one or more hardware components for the implementing a control system as described above, for example an IC chip, adapted to implement a method according to the invention.
Optionally, the computer readable memory includes machine readable code to receive input of or compute for each of a group of respective time points of interest T1 . . . Tcurrent) each in turn a respectiveTcurrent:
The computer readable memory may also include machine readable code for controlling a gas delivery means (GDn) so that the actual incremental volume of CO2 coordinately delivered with CVG0 (as part of CVGR) targets FCO2T(for example, any suitable controller known to those skilled in the art, for example, a PI or PID controller).
In another aspect, the present invention is directed to a device (an IC chip), CPU or microcontroller programmed to implement one or more embodiments of the above method. The program may include machine readable code as defined above. The program may be recorded on an integrated or external computer readable memory.
The aforesaid device may optionally include the following: the VCn and optionally, one or more components which serve one or more functions of: a VSn, GDn and optionally a Gn gas channeling means for example a port or Gn gas delivery conduit for receiving the Gn delivered by the GDn.
Accordingly, according to another aspect, the invention is directed to a device for adding at least one added gas (Gn) to an inspiratory gas G0, to formulate a respiratory gas (GR) for delivery to a subject, and maintaining a targeted concentration of CO2 in the GR, comprising: a processing unit programmed to implement the method defined hereinabove (optionally, a CPU, microprocessor or microcontroller or dedicated circuit) and optionally, the VCn and optionally, the VSn, GDn and a Gn gas channeling means, for example a Gn gas delivery conduit, for channeling the Gn output by the GDn.
The Gn gas channeling means, optionally in the form of Gn delivery conduit is optionally adapted to be operatively associated with or directly fluidically connected to a G0 or GR gas channeling means, for example a G0 or GR delivery conduit (e.g. an inspiratory limb of a breathing circuit) or any other gas channeling means e.g. a dedicated limb of a breathing circuit, a patient airway interface, a manifold, for example, a manifold for receiving multiple added gases or a connector interconnecting one or more of the above. Optionally, the device also includes a volume sensor (VS0) operatively associated with the device for determining a cumulative volume of G0 (or a volume sensor (VSR) operatively associated with the device for determining a cumulative volume of inspired respiratory gas). The device optionally includes a G0 channeling means e.g. a G0 delivery conduit for delivering an inspiratory gas (G0) to a subject. The term “delivery” to describe a conduit is used to in the sense of “channel” and does not imply the capacity to move a gas without a GDn. Similarly, the termed “delivered” in the context of outcome of channeling a gas does not imply the capacity to move the gas into the patient's lung, but simply releasing a certain volume of gas to be available for spontaneous inhalation or to be moved by a ventilator.
In another aspect, the invention is directed to a respiratory gas delivery system for delivering a respiratory gas to a subject including a G0 delivery system, for example a breathing circuit, a ventilator (manual or mechanical), an anesthetic machine etc.) and a Gn delivery system incorporating one or more the features of a device or method as defined herein.
Accordingly in another aspect the invention is directed to a system for adding a carbon dioxide containing gas Gn to an inspiratory gas (G0) stream, to formulate a respiratory gas GR, comprising:
The term computer is used broadly to refer to any device (constituted by one or any suitable combination of components) which may used in conjunction with discrete electronic components to perform the functions contemplated herein, including computing and obtaining input signals and providing output signals, and optionally storing data for computation, for example inputs/outputs to and from electronic components and application specific device components as contemplated herein. As contemplated herein a signal processor, processor or processing device (these terms used broadly and interchangeably unless a narrower meaning is implicit and means a CPU or computer in any suitable form) e.g. in the form of a computer may use machine readable instructions or dedicated circuits to perform the functions contemplated herein including without limitation by way of digital and/or analog signal processing capabilities, for example a CPU, for example a dedicated microprocessor embodied in an IC chip which may be integrated with other components, for example in the form of a microcontroller. Key inputs may include input signals from—a volume sensor such as a flow meter, a gas analyzer, any type of input device for inputting a CO2T (for example, a knob, dial, keyboard, keypad, mouse, touch screen etc.) input from a computer readable memory etc. Key outputs include output of a control signal to control to a GDn, including any control signal from a VCn based on an en to target CO2T, for example PI control or PID control, an output signal to an alarm generating device etc. A variety of alternative forms of suitable control signals for controlling GDn are well known to those skilled in the art.
In one aspect, a Gn delivery system according to the invention is part of a larger respiratory gas delivery system including a G0 channeling means (for example a port or conduit for conducting the G0, for example, forming part a manifold and/or one or more parts of a breathing circuit e.g. an inspiratory limb of a breathing circuit) and a volume sensor for obtaining input to determine a cumulative amount or G0 or GR delivered. Optionally, a Gn delivery system is an adjunct device which includes Gn delivery components but does not include one or both of the first gas channeling means (e.g. a conduit or dedicated port) for delivering an inspiratory gas (G0) to a subject or a volume sensor. The invention contemplates that a device according to the invention may nevertheless receive output from a volume sensor (VS0) which is operatively associated with the device for determining a cumulative volume of inspired G0 (or an equivalent volume sensor (VSR) operatively associated with the device for determining a cumulative volume of delivered respiratory gas). The Gn channeling means e.g. a port in a manifold or a delivery conduit (alternatively called an “added gas delivery conduit”) may be readily adapted to be operatively associated with (e.g. connected to—the first gas delivery conduit or an airway interface (e.g. a mask, endotracheal tube etc. that interfaces with the subject's airway) in a manner suitable for channeling Gn to the subject in tandem with the G0. The device computer may be programmed to receive inputs of the VS0. or VSR optionally in the form of a computed cumulative volume for use according to the invention or directly in the form of incremental volumes from which the device computer computes the requisite cumulative volumes.
The term “operatively associated” is generally (unless the context dictates otherwise) used expansively to mean “functionally associated”, whether directly or indirectly, for a specified or implicit purpose. For example, a sensor will be operatively associated with the first gas (G0) delivery conduit if it directly measures the volume of gas moving through the conduit at a selected time point or indirectly measures the volume of gas by measuring the combined volume of the Gn and G0 moving into a subject airway interface and subtracting the volume of Gn.
In one embodiment of the devices described above, the output from a volume controller VCn is a based on PID control algorithm, for example an error signal for a respective Tcurrent is generated based a weighted sum of en for the respective Tcurrent, the derivative of en for the respective Tcurrent and the integral of en for the respective Tcurrent.
Depending on the application, the cumulative inspired volume of respiratory gas may be constituted by the volume of a part of an inspiratory cycle, a full inspiratory cycle or a series of, parts of or full, inspiratory cycles.
In one embodiment of a device according to the invention the second gas channeling means (e.g. a second gas delivery conduit or added gas delivery conduit) may be fluidly connected to the gas channeling means (optionally a first gas delivery conduit) to deliver Gn into the first gas channeling means e.g. delivery conduit. Alternatively, the first gas channeling means and the second gas channeling means are independently connected to a subject airway interface for coordinately delivering G0 and Gn respectively into the subject airway interface.
It will be appreciated that each of the key method steps for carrying out the invention can be functionally apportioned to different physical components or different computer program products or combinations of both. Furthermore a device according to the invention may comprise one or more physical components in the form of sensors (e.g. flow), gas delivery devices, gas analyzers, gas channeling means, standard electronic components making up a PCB, input devices for setting parameters etc. The various means for carrying out these steps include without limitation one in the same physical means, or different physical means on different devices, the same device or the same device component. Depending on the number of added gases these components may multiplied or where possible shared. A device which is directed to implementing a method of preparing a carbon dioxide (CO2)-containing gas (Gn) that is organized for delivery in tandem with a second gas (G0), in manner that composes a respiratory gas (GR) and maintains a target CO2 concentration (FCO2T) in a cumulative volume of the GR of interest (CVGRI), may comprise:
for each successive time point of interest in a growing time period comprising all time points of current interest T1 to Tlast, each successive time point in turn a Tlast:
In at least one general aspect, the invention is directed to a method for adding at least one added gas (Gn) to an inspiratory gas G0, to formulate a respiratory gas (GR) for delivery to a subject, and to maintain a targeted concentration of at least one component of an added gas Gn (DAn) in a volume of the GR (DART), comprising the steps of:
Each of the individual embodiments of the invention described herein may be adapted to implement the method described immediately above.
In at least one general aspect, the invention is directed to an apparatus for adding at least one added gas (Gn) to an inspiratory gas G0, to formulate a respiratory gas (GR) for delivery to a subject, and to maintain a targeted concentration of at least one component of an added gas Gn (DAn) in a volume of the GR (DAnT), comprising:
Each of the individual embodiments of the invention described herein may be adapted to assemble or implement the apparatus defined immediately above.
The term “inspiratory gas” denoted G0 refers to any gas to which a gas consisting of or comprising a gas of interest (a component gas) is added. The G0 may be a principal gas provided to a subject for inhalation. For example, a ventilated patient may receive oxygen enriched gas as the G0. The G0 may also be one or more gases consisting or comprising desired component gases which may be individually or collectively considered a G0 with reference to another component gas. Accordingly the invention is concerned with but not limited to conditioning an inspiratory gas in the sense only of a principal gas and in one embodiment of the invention several added gases may be channeled into a manifold and each or the combination of several of them may be an inspiratory gas with reference to a particular component gas. Therefore, the invention contemplates that the necessary volumetric information is ascertained to track actual volumes of the component gas(es) of interest and the volume of gas e.g. the G0 or GR into which a component gas has been diluted.
The term “volume sensor” (which may also be referred to as a “volume sensing means”) means any device that can be used to directly or indirectly determine the volume of a gas that has passed through a breathing circuit or particular conduit thereof, typically with respect to a reference location in a breathing circuit. The invention contemplates that this can be accomplished by a variety of types of hardware including a flow meter, a gas concentration sensor (for example, a certain amount of any first gas of known composition can be inferred to have been delivered past a reference point if mixed with any second gas of known composition and volume by ascertaining the concentration of the first gas in a mixture of the first and second gases), a pressure transducer (for example, an added gas is sourced from a tank of fixed volume, and a pressure transducer in the tank could be used to determine the volume obtained from the tank).
As shown in
As shown in
In one embodiment illustrated, for example in
As shown in
A device according to the invention may therefore comprise a wider or narrower variety of components that may be particularly useful or more readily substitutable for implementing a particular application of the invention. Furthermore, depending on a suitable range of deliverable volumes of gas in question, optionally attuned to a particular size range of a breath (e.g. for a premature human infant or small animal) the sizes and ranges of accuracy of components may be differently selected according to well understood design criteria.
In terms of optional embodiments, the GDn is optionally a proportional solenoid valve metering the release of Gn from a pressurized gas source. The invention also encompasses intermittently turning on and off a two-way solenoid valve metering the release of Gn from a pressurized gas source. Optionally, the GDn can be a gas pump, blower, or injector connected to a pressurized or unpressurized reservoir of Gn.
Input of CVGn actually delivered during T1 . . . Tnow is obtained via a volume sensor (VSn) operatively associated with a Gn delivery conduit. Input of CVG0 actually delivered during T1 . . . Tnow may be obtained via a second volume sensor (VS0) operatively associated with a G0 delivery conduit. A volume sensor can be constituted by any hardware for directly or indirectly measuring a volume of gas, for example, a spirometer, or a flow transducer or gas analyzer from which the flows of gases can be deduced (and then computing the integral of the flow).
The inputs, computations, and outputs described in the aforementioned method can be carried out by a variety of signal processing means including, but not limited to, a programmable processor, programmable microcontroller, dedicated integrated circuit, programmable integrated circuit, discrete analog or digital circuitry, mechanical components, optical components, or electrical components.
The VCn can be implemented by a variety of signal processing means including, but not limited to, a programmable processor, programmable microcontroller, dedicated integrated circuit, programmable integrated circuit, discrete analog or digital circuitry, mechanical components, optical components, or electrical components.
A Gn gas channeling means, optionally in the form of a Gn delivery conduit, is optionally adapted to be operatively associated with or directly fluidically connected to a G0 channeling means, for example, a G0 delivery conduit such as the inspiratory limb of a breathing circuit, a patient airway interface, a manifold for receiving multiple gas connections, or a connector interconnecting one or more of the above.
In one embodiment of the invention, all inputs, computations, and outputs are performed on a general purpose microcontroller. The Gn is a pressurized gas containing a known, fixed concentration of DAn. A rapid DAn analyzer is operatively associated with the G0 delivery conduit to ascertain the concentration of DAn in G0. A VSn is implemented by integrating the output of a flow transducer operatively associated with the Gn delivery conduit. A VS0 is implemented by integrating the output of a flow transducer operatively associated with the G0 delivery conduit. The VCn may be a PID controller implemented on a general purpose microcontroller. For each Tcurrent, GDn receives a weighted sum of the output of VCn and GnP. The incremental G0P predicted to be delivered in the time interval ΔT between the respective Tcurrent and a ensuing time point Tcurrent+ is equated with the incremental volume of G0 delivered in the time interval ΔT ending at Tcurrent. The GDn is implemented with a series of pressure regulators and a proportional solenoid valve metering the release of Gn from the pressurized source. The Gn delivery conduit is directly fluidically connected to the G0 channeling means so that the Gn is directly delivered into the G0 stream.
As shown in
VDAn (represented by the oval area 40) is an accumulated volume of the component gas of interest that forms part of the volume of GR 20 delivered in virtue of being added at full concentration (Gn is 100% DAn) or blended (as illustrated) into one or more of V1, V2 . . . Vn. DAn may optionally also be a component of inspiratory gas G0. An error signal en according to a simple embodiment of the invention is the volume 10 of gas Gn that is needed to be delivered (based on what on has been “definitively” already delivered) to carry with it enough of the component gas of interest to ensure that the resulting amount of this component gas in a volume of the respiratory gas GR is incrementally maintained (subject to hardware time lags) and therefore consistently (to the extent practicable or desired) in the same proportion vis-à-vis the total volume of “definitively” delivered GR regardless of the changing total volume of gas that has been delivered to the subject. “Definitively” delivered amounts of Gn and GR are not amounts that the hardware would have delivered if responding perfectly to flow settings but volumes that requisite “sensors” determine have indeed flowed through the pertinent gas delivery conduits. The term “definitively” is used superfluously in the present description of
It may be appreciated that the strategy of the invention may be implemented to a useful extent if the incremental gas proportioning is consistent in the first part of inspiratory cycle (see
As shown in
The term DAn (and, as applicable, terms which reference DAn such as FDAn and CVGDAn) may for convenience be understood to be used expansively to reference embodiments of the invention in which there is one DAn as well as multiple DAns (more precisely DA1-n) since DAn in the latter scenario can be understood, if interpreted in a restrictive sense, to mean the last in the series 1 to n. In context, where more than one “DAn” is delivered as part of the cumulative volume of respiratory gas GR, with respect to each “DAn” (strictly speaking each respective DA1 . . . DAD), each other “DAn” can be understood to be taken into account as part of the G0 and hence the aforementioned generic formula for the error term en should be understood broadly to be generically applicable to each respective “DAn” (DA1 . . . n) based on the assumption that the volumes of the added gases other than the one for which the computation is being made are taken into account as part of the G0. The (+) sign with reference to a time point is used herein to refer to a future time point (not yet a Tcurrent) for which actual delivered (output by a Gn specific gas delivery device or ventilator) volumes of a component gas and G0/GR have not been ascertained. A minus (−) sign may be used to refer to a time point before a respective Tcurrent e.g. the most recent Tcurrent for which actual delivered (output) volumes have been ascertained.
It will be appreciated from the foregoing description that en may be a corrective volume to bring the concentration of DAn in line with DAnT as at Tcurrent without taking into account the incremental volume of G0 expected to be delivered by the next respective Tcurrent+1. Alternatively, the computation may take into account the expected incremental volume of G0 expected to be delivered by the next respective Tcurrent+ and hence the projected total of volume of respiratory gas expected to be delivered by the next Tcurrent including the en and its DAn content.
As shown in
In one aspect, the volume of gas containing DAn is ideally delivered as part of the expanding volume of gas that is alveolar gas and not dead space gas. This is explained with reference to
The invention can therefore be understood to be broadly directed to a method for adding at least one added gas (Gn) to an inspiratory gas G0, to formulate a respiratory gas (GR) for delivery to a subject, and to maintain a targeted concentration of at least one component of an added gas Gn (DAn) in a volume of the GR comprising the steps of:
for each of a series of time points of interest (generally time points in which Gn is being coordinately delivered with G0):
Thus in a broader aspect, the present invention relates to a device, method and system for delivering at least one added gas into an inspiratory gas stream to formulate a blended respiratory gas in a manner that continuously maintains a target concentration of the added gas in a volume of inspired respiratory gas, for example, over the course of a breath or a volumetrically definable part thereof or a series of partial or full breaths. The inspiratory gas may be a principal gas stream delivered to a patient such as air optionally having an enhanced oxygen content or air and oxygen combined with an anesthetic gas delivered by a ventilator or anesthetic machine but may also be comprised of several additive gases delivered individually or in blended form according to a method/device according to the invention.
A goal of most respiratory gas blenders is to deliver a target concentration of an additive gas into the inspired stream. Previously, this has been done by measuring the inspiratory flow and sending a signal to a flow controller to provide a flow of additive gas proportional to the inspired stream. Such a “flow-based control” system essentially tries to maintain the instantaneous concentration of the additive gas in the inspired gas at the target value. However, due to practical limitations of flow transducers and flow controllers, most notably finite response times, it is not possible for a flow controller to exactly “track” the inspired gas stream. Therefore, at any time during the breath, the instantaneous concentration of additive gas in the inspired stream may not be equal to the target concentration. Moreover, the overall concentration of additive gas in the accumulated inspired volume will not be equal to the target concentration. Furthermore, the design of previous respiratory gas blending systems overlooks that it is the concentration of additive gas, by volume, in the volume of inspired gas that reaches the alveoli that is the most important factor in many physiologic, therapeutic and/or diagnostic contexts.
The simplest gas blending systems try to match the flow of additive gas to the inspired stream with an open loop signal to a flow controller. That is, the actual flow of additive gas delivered by the flow controller is not monitored. If there is a systematic error/offset in the flow delivered by the flow controller, the flow of additive never reaches the target flow rate. Therefore, the instantaneous concentration of additive in the inspired stream never reaches target, and the concentration by volume in the accumulated inspired gas is always in error.
More complex blending systems try to match the flow of additive gas into the inspiratory gas stream with a closed loop signal to a flow controller. That is, the actual flow of additive gas delivered by the flow controller is monitored. If there is a systematic error/offset in the flow delivered by the flow controller, the signal to the flow controller is adjusted until the flow of additive reaches the desired flow rate. Therefore, the concentration of additive in the inspired stream may reach the target value as the breath proceeds, but because of an obligatory delay in response of the flow controller for the additive gas, the overall concentration by volume will always be less than the target concentration set at the beginning of the breath.
In one aspect, the present invention contemplates a control system in which the overall concentration of additive gas, in the volume inspired gas entering into the alveoli, reaches the desired value.
The invention contemplates that one or more additional gas delivery conduits may be operatively connected to or otherwise operatively associated with (via coordinated delivery into an airway interface) the G0 delivery conduit for coordinately delivering a controlled volume of an added gas Gn (or controlled volumes of a plurality of added gases G1 to Gn) with the G0 stream, wherein each G1-n is at least partially composed of a respective desired additive gas (DA1-n). In one embodiment, each gas delivery conduit carrying an added gas is operatively associated with a volume controller for controlling the volume of gas coordinately delivered with the G0, a volume sensor operatively associated with the added gas delivery conduit for continuously measuring the accumulated volume of the added gas. Optionally, where the fractional concentration of the added gas in G0 is not known, a means (for example a gas analyzer), operatively associated with the G0 delivery conduit, may be employed to measure, optionally continuously, the fraction of the added gas in the G0 delivery conduit. Optionally, for example for a given Gn, where the fractional concentration of the desired added gas in Gn (FDAn) is not known, a means, operatively associated with the Gn delivery conduit, for example a gas analyzer may be employed to measure, optionally continuously, FDAn in the Gn delivery conduit (GSn). For example, in one embodiment, for a gas Gn, the device may comprise:
On inspiration, gas entering the mouth or nose is conducted to the lung through a series of conduits consisting nasopharynx, oropharynx, trachea and bronchi. From the point of view of gas exchange, these are considered conducting vessels directing gas to the alveoli. As these conducting vessels do not contribute substantially to gas exchange, they are termed anatomical deadspace. In an average adult, they consist of about 2 ml per kg of body mass, or about 150 ml for the average adult. The alveoli are small saccules where the gas comes into close contact with blood and gas exchange takes place.
The distribution of gas during inspiration is well understood. At end expiration, the lung volume is smallest. In the course of inhalation gas is drawn through the anatomical deadspace into the alveoli. At end inspiration, the inspired gas is distributed between the alveoli and the anatomical deadspace. Note the last inhaled gas is retained in the anatomical deadspace. Physiologically the alveoli acts like a mixing chamber where the accumulated gases are mixed. The physiologic effect of an inhaled gas is determined by its net concentration once it has mixed in the alveolar space, that is, its fractional volume in the alveoli. Its instantaneous inhaled concentration is only important to the extent that it affects the net volume of that gas in the inspired volume. Although the flow-based controllers can reach an instantaneous target concentration of additive in the inspired stream, they are not directed towards providing a net concentration of a gas in the alveolar space where gas exchange takes place and where the net concentration of the added gas exerts its pharmacologic effect. This is illustrated in
Previous devices have been designed on the premise that a response delay of a flow-based controller at the start of the breath is mirrored by an overshoot in G1 flow at the termination of the breath. Over the whole breath, this may result in an average alveolar G1 concentration at the desired level if the acceleration and deceleration profile of the breath are symmetrical. However with respect to ventilation, as illustrated in the lower part of
By contrast, a closed loop volume-based control provides early reconciliation of the G1 volume and the inspired volume of G0 such that the net inspired concentration of G1 is at the desired level very early in the breath. In practical terms, a volume controller according to the invention can provide fully compensated alveolar concentrations of G1 within as little as 10 ml of inspired volume and typically within 20-50 ml. Premature terminations of breaths after this level is reached would not affect the physiologically important net inspired concentration of G1 in the alveolar compartment of the lung.
Furthermore, with respect to the finite response time of any flow controller, the shorter the breath, and the greater the inspiratory flow, the more significant the delay period of the flow controller becomes with respect to providing the overall volumetric concentration of additive gas. Therefore for rapid breathing, where inspiratory flows are high and inspiratory times short, errors of DAn volumetric concentrations in the alveoli are magnified by response delays of flow controllers. Furthermore, even flow controllers with very rapid response times may still accumulate physiologically important errors of concentrations of DAn, particularly where DAn is a potent physiologic molecule (defined as having a large physiologic effect for a small change in concentration), in the overall volumetric concentration of DAn in the accumulated inspired volume.
The system according to the invention operates a closed control loop in order to maintain the concentration of additive, by volume, in the accumulated inspired volume at a target value throughout the breath. At each point in time, the total inspired volume and the total volume of inspired additive is assessed. An error signal is generated equal to the volume of additive that must be added to the inspiratory gas stream so that the overall concentration of additive, by volume, in the gas accumulated in the lung during inspiration will be equal to the target value throughout the breath. The error signal is provided to a volume controller which provides a signal to a gas delivery means (alternatively called a gas delivery device). This maintains the concentration of additive, by volume, in the accumulated inspired volume at the target value throughout the breath.
As described below, the invention contemplates that multiple gases can be combined according to a method of the invention or using a device, computer program product (including any known format in which the requisite program code can be recorded or hard-wired), processor or system according to the invention based on adaptations described herein and evident to those skilled in the art. A reference to blending or delivering a Gn in tandem with a G0 that does not explicitly specify a single Gn and that can be understood to be a general case in which there is more than one added gas having the same or a different component gas of interest are meant to disclose this general case of the invention in which permutations and adaptations to accommodate more than one added component are understood to be related. Furthermore each of the general classes and specific embodiments of the invention are meant to refer back to the variety of aspects of the invention described herein and any logistical permutation of these various classes of and specific embodiments are understood to be described within the general concepts for implementing the invention elaborated above. Therefore, while a number of exemplary aspects and embodiments have been discussed above, those of skill in the art will recognize certain modifications, permutations, additions and sub-combinations thereof. It is therefore intended that the foregoing description and following appended claims and claims hereafter introduced are interpreted to include all such modifications, permutations, additions and sub-combinations as are within their true spirit and scope. Alternative terms for any features, elements, components etc of the invention as defined herein are not meant to be differentiated by virtue of the use of alternative language and each term is intended to be given its broadest meaning consistent with the context and the function it serves according the description of the invention as a whole. The scope of the claims should not be limited by the preferred embodiments, but should be given the broadest interpretation consistent with the description of the invention as a whole.
The present application is a continuation of co-pending U.S. patent application Ser. No. 14/111,993, filed Nov. 15, 2013, which is a national phase filing, under 35 U.S.C. § 371(c), of International Application No. PCT/CA2012/000351, filed Apr. 12, 2012, the disclosures of which are incorporated herein by reference as if set forth in full herein. International Application No. PCT/CA2012/000351, in turn, claims the benefit, under 35 U.S.C. § 119(e), of U.S. provisional application Ser. No. 61/475,106, filed on Apr. 13, 2011, the disclosure of which is incorporated herein by reference in its entirety.
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| Number | Date | Country | |
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| Number | Date | Country | |
|---|---|---|---|
| Parent | 15405069 | Jan 2017 | US |
| Child | 16781665 | US | |
| Parent | 14111993 | US | |
| Child | 15405069 | US |
