# US 11,077,266 B2 · Method and apparatus to attain and maintain target arterial blood gas concentrations using ramp sequences

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- Number: US 11,077,266 B2
- Document ID: US11077266B2
- Status: Granted
- Kind: B2
- Application number: 15/904,235
- Filed: 2018-02-23
- Published: 2018-11-01
- Granted: 2021-08-03
- Earliest claimed: 2012-04-30
- Assignees: Thornhill Scientific Inc.
- Applicants: Thornhill Scientific Inc.
- Inventors: Michael Klein; Joseph Fisher; James Duffin; Marat Slessarev; Cathie Kessler; Shoji Ito; Olivia Sobczyk; Anne Battisti-Charbonney; Daniel Michael Mandell
- Web page: https://patentgrep.com/patent/US11077266B2

## CPC

- A61M 16/0066: {Blowers or centrifugal pumps}
- A61M 16/0045: {Means for re-breathing exhaled gases, e.g. for hyperventilation treatment}
- A61M 16/026: {specially adapted for predicting, e.g. for determining an information representative of a flow limitation during a ventilation cycle by using a root square technique or a regression analysis}
- A61M 16/1005: {with O2 features or with parameter measurement}
- A61M 16/12: by mixing different gases
- A61M 16/122: {with dilution}
- A61B 5/082: {Evaluation by breath analysis, e.g. determination of the chemical composition of exhaled breath (A61B5/083, A61B5/091 take precedence)}
- A61B 5/091: Measuring volume of inspired or expired gases, e.g. to determine lung capacity
- A61M 2016/0027: {pressure meter}
- A61M 2016/0036: {in the breathing tube and used in both inspiratory and expiratory phase}
- A61M 2016/1025: {the O2 concentration}
- A61M 2016/103: {the CO2 concentration}
- A61M 2202/0208: Oxygen
- A61M 2202/0225: Carbon oxides, e.g. Carbon dioxide
- A61M 2205/3303: Using a biosensor
- A61M 2205/502: User interfaces, e.g. screens or keyboards
- A61M 2205/52: with memories providing a history of measured variating parameters of apparatus or patient
- A61M 2230/04: Heartbeat characteristics, e.g. ECG, blood pressure modulation
- A61M 2230/202: partial carbon oxide pressure, e.g. partial dioxide pressure (P-CO2)
- A61M 2230/205: partial oxygen pressure (P-O2)
- A61M 2230/208: pH-value
- A61M 2230/432: partial CO2 pressure (P-CO2)
- A61M 2230/435: partial O2 pressure (P-O2)
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)

## Abstract

An apparatus and method for controlling the end tidal partial pressure of a gas X in a subject's lung, and to the use of such an apparatus and method for research, diagnostic and therapeutic purposes, wherein the method consists of: —obtaining input of a series of logistically attainable PetX values for a series of respective breaths: —determining an amount of gas X required to be inspired by the subject in an inspired gas to target the PetX for each of said respective breaths: and—controlling a gas delivery device to deliver the amount of gas in a volume of gas delivered to the subject in each of said respective breaths to target the respective PetX for that breath.

## Claims

### Claim 1

An apparatus for controlling an amount of at least one gas X in a subject's lung to attain a series of targeted end tidal partial pressures of the at least one gas X (PetXT), the series of targeted end tidal partial pressures of the at least one gas X (PetXT) selected to stimulate a physiological response, the apparatus comprising:
(1) a gas delivery device;
(2) a control system for controlling the gas delivery device, wherein the control system is adapted to target a series of PetXT values for a series of respective breaths [i], the series of PetXT values comprising at least one of a set of PetXT increments and a set of PetXT decrements, the control system including means for:
a. obtaining input of a series of logistically attainable PetXT values for the series of respective breaths [i];
b. performing a prospective computation of an amount of gas X required to be inspired by the subject in an inspired gas to target the PetXT for a respective breath [i], the performing comprising:
i. computing a mass balance equation including input of the concentration of gas X in the mixed venous blood entering the subject's pulmonary circulation for gas exchange in a respective breath [i] (CMVX[i]); and
ii. outputting one or more values required to control the amount of gas X in a volume of gas delivered to the subject, based on the mass balance equation; and
c. controlling the amount of gas X in a volume of gas delivered to the subject in a respective breath [i] to target the respective PetXT for the breath [i];
wherein at least one of a length and a number of breaths [i] in the series of respective breaths [i] is selected to show a pattern of the subject's physiological response including a dose response to the at least one of the set of PetXT increments and the set of PetXT decrements.

### Claim 2 (depends on 1)

The apparatus of claim 1, wherein the at least one gas X includes carbon dioxide (CO2) and wherein the physiological response is a vasodilatory response, wherein at least a set of logistically attainable PetCO2T increments representing a desired range of a vasoactive stimulus is input in step a. to attain a series of PetCO2T values for the series of respective breaths [i], and wherein the series of breaths [i] are selected to satisfy a condition, the condition defined by at least one of a predicted and measured attainment of at least a minimum increment in the subject's vasodilatory response to an increment in the subject's end tidal partial pressure of carbon dioxide.

### Claim 3 (depends on 1)

The apparatus of claim 1, wherein the prospective computation relies on a tidal model of the lung.

### Claim 4 (depends on 1)

The apparatus of claim 1, wherein the mass balance equation is computed in terms of discrete respective breaths [i] including one or more discrete volumes corresponding to a subject's functional residual capacity, anatomic dead space, a volume of gas transferred between the subject's lung and pulmonary circulation in the respective breath [i] and an individual tidal volume of the respective breath [i].

### Claim 5 (depends on 1)

The apparatus of claim 1, where the physiologic response over the time course of the response is exponential, and wherein a rate of change in PetXT is selected such that three time constants in the progress of the response are achieved before a next breath [i].

### Claim 6 (depends on 1)

The apparatus of claim 1, where the physiologic response over its time course is exponential, and wherein a rate of change in PetXT is selected such that three time constants in the progress of the response are achieved before a next breath [i].

### Claim 7 (depends on 1)

The apparatus of claim 1, wherein the control system, in each respective breath [i], controls the delivery of at least a first inspired gas and wherein delivery of the first inspired gas is coordinated with delivery of a second inspired neutral gas, wherein a selected volume of the first inspired gas is delivered in the first part of the respective breath [i] followed by the second inspired neutral gas for the remainder of the respective breath [i], wherein volume of the first inspired gas is fixed or selected for one or more sequential breaths by way of user input so that intake of the second inspired neutral gas at least fills the entirety of the anatomic dead space.

### Claim 8 (depends on 1)

The apparatus of claim 1, wherein the gas delivery device is a gas blender.

### Claim 9 (depends on 1)

The apparatus of claim 1, wherein the gas X is CO2.

### Claim 10 (depends on 9)

The apparatus of claim 9, wherein a series of PetCO2 targets provide a series of controlled vasoactive stimuli for measurement of vascular reactivity.

### Claim 11 (depends on 10)

The apparatus of claim 10, wherein the series of PetCO2 targets provide at least one of the following:
a) a controlled as active stimulus for measurement of cerebrovascular reactivity;
b) a controlled vasoactive stimulus for measurement of liver, kidney, heart or eye vascular reactivity;
c) a simultaneous change in the subject's end tidal partial pressures of oxygen and carbon dioxide to selected values, to potentiate a diagnosis or to treat cancer; and
d) a controlled vasoactive stimulus for diagnosing steno-occlusive-disease.

### Claim 12 (depends on 1)

The apparatus of claim 1, wherein a respective PetX[i]T for a series of breaths [i] increases every Nth breath in respective selected increments (“Z”) from the start of the series to the end of the series (from PetX[i1]T to PetX[in]T), wherein either N equals 1 and Z is greater than 0 in each breath in the series, or N is greater than 1 and Z may be zero in breaths which are not the Nth breath and Z is greater than 0 in every Nth breath.

### Claim 13

A computer program product for use in conjunction with a gas delivery device to control an amount of at least one gas X in a subject's lung to attain a series of target end tidal partial pressure of the at least one gas X (PetXT) selected to stimulate a physiological response, the computer program comprising program code for:
a. obtaining input of a series of logistically attainable end tidal partial pressure of gas X (PetXT) for a respective breath [i]; and
b. performing a prospective computation to obtain input of an amount of gas X required to be inspired by the subject in an inspired gas to target the PetX[i]T based on the input, the performing comprising:
i. computing a mass balance equation including input of the concentration of gas X in the mixed venous blood entering the subject's pulmonary circulation for gas exchange in a respective breath [i] (CMVX[i]); and
ii. outputting one or more values required to control the amount of gas X in a volume of gas delivered to the subject, based on the mass balance equation;
wherein at least one of a length and a number of breaths [i] is selected to disclose a pattern of a physiologic response to the series of targeted end tidal partial pressures of the at least one gas X.

### Claim 14

A method for controlling an amount of at least one gas X in a subject's lung to attain a series of targeted end tidal partial pressures of at least one gas X (PetXT), the method comprising:
a. obtaining input of a series of logistically attainable PetXT values for a series of respective breaths [i] comprising at least one of a set of PetXT increments and set of PetXT decrements; and
b. performing a prospective computation of an amount of gas X required to be inspired by the subject in an inspired gas to target the respective PetXT for the breath [i], the performing comprising:
i. computing a mass balance equation including input of the concentration of gas X in the mixed venous blood entering the subject's pulmonary circulation for gas exchange in a respective breath [i] (CMVX[i]); and
ii. outputting one or more values required to control the amount of gas X in a volume of gas delivered to the subject, based on the mass balance equation;
wherein at least one of a length and a number of breaths [i] in the series of respective breaths [i] is selected to disclose a pattern of a physiologic response to the series of targeted end tidal partial pressures of the at least one gas X.

### Claim 15 (depends on 14)

The method of claim 14, wherein each breath [i] is a respective breath [i] and wherein a respective PetX[i]T for the series of breaths [i] increases every Nth breath in respective selected increments (“Z”) from the start of the series to the end of the series (from PetX[i1]T to PetX[in]T), wherein either N equals 1 and X is greater than 0 in each breath in the series, or N is greater than 1 and Z may be zero in breaths which are not the Nth breath and Z is greater than 0 in every Nth breath.

### Claim 16 (depends on 14)

The method of claim 14, wherein the physiologic response over the time course of the response is exponential, and wherein a rate of change in PetXT is selected such that two time constants in the progress of the response are achieved before a next breath [i].

### Claim 17 (depends on 14)

The method of claim 14, wherein the physiologic response over the time course of the response is exponential, and wherein a rate of change in PetXT is selected such that three time constants in the progress of the response are achieved before a next breath [i].

### Claim 18 (depends on 14)

The method of claim 14, wherein the gas X is CO2 and wherein a series of PetCO2 targets provide a series of controlled vasoactive stimuli for measurement of vascular reactivity.

### Claim 19 (depends on 14)

The method of claim 14, wherein X is CO2 and wherein a series of PetCO2 targets provide a series of controlled vasoactive stimuli for measurement of at least one of the following:
a) a controlled vasoactive stimuli for measurement of cerebrovascular reactivity;
b) a controlled vasoactive stimulus for measurement of liver, kidney, heart or eye vascular reactivity;
c) a simultaneous change in the subject's end tidal partial pressures of oxygen and carbon dioxide to selected values, for example to potentiate a diagnosis or to treat cancer; and
d) a controlled vasoactive stimulus for diagnosing steno-occlusive-disease.