Method and apparatus to attain and maintain target arterial blood gas concentrations using ramp sequences

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.

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 (PetX T ), the series of targeted end tidal partial pressures of the at least one gas X (PetX T ) 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 programmed to target a series of PetX T  values for a series of respective intervals, the series of PetX T  values comprising at least one of a set of PetX T  increments and a set of PetX T  decrements, the control system including means for:
 a. Obtaining input of a series of logistically attainable PetX T  values for the series of respective intervals; and 
 b. Determining an amount of gas X required to be inspired by the subject in an inspired gas to target the PetX T  for a respective interval; 
 c. Controlling the amount of gas X in a volume of gas delivered to the subject in a respective interval to target the respective PetX T  for the interval; 
   wherein at least one of the size and the number of intervals is selected to reveal a pattern of the subject's physiological response including a dose response to the at least one of the set of PetX T  increments and the set of PetX T  decrements.   
     
     
         2 . An apparatus as claimed in  claim 1 , wherein each interval is a respective breath [i]. 
     
     
         3 . An apparatus as claimed in  claim 1 , wherein the at least one gas X includes carbon dioxide (CO 2 ) and wherein the physiological response is a vasodilatory response and wherein at least a set of logistically attainable PetCO 2   T  increments representing a desired range of a vasoactive stimulus is input in step a. to attain a series of PetCO 2   T  values for the series of respective intervals, and wherein the series of intervals 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. 
     
     
         4 . An apparatus as claimed in  claim 1 , wherein each interval is a respective breath [i] and wherein the control system is configured to perform a prospective computation of an amount of gas X required to be inspired by the subject in an inspired gas to target the PetX[i] T  for a respective breath [i] using inputs required to compute 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] (C MV X[i]), wherein values required to control the amount of gas X in a volume of gas delivered to the subject is output from the mass balance equation based on the prospective computation. 
     
     
         5 . An apparatus as claimed in  claim 4 , wherein the prospective computation relies on a tidal model of the lung. 
     
     
         6 . An apparatus as claimed in  claim 4 , 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 FRC, 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]. 
     
     
         7 . An apparatus as claimed in  claim 2 , wherein the 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[i 1 ] T  to PetX[i n ] 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. 
     
     
         8 . An apparatus as claimed in  claim 1 , where the physiologic response over the time course of the response is exponential, and wherein the rate of change in PetX T  is selected such that two time constants in the progress of the response are achieved before a next interval. 
     
     
         9 . An apparatus as claimed in  claim 1 , where the physiologic response over its time course is exponential, and wherein the rate of change in PetX T  is selected such that three time constants in the progress of the response are achieved before a next interval. 
     
     
         10 - 15 . (canceled) 
     
     
         16 . An apparatus as claimed in  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 a second inspired neutral gas, wherein a selected volume of the first inspired gas is delivered in the first part of a 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 fill the entirety of the anatomic dead space. 
     
     
         17 . (canceled) 
     
     
         18 . An apparatus as claimed in  claim 1 , wherein the gas delivery device is a gas blender. 
     
     
         19 . (canceled) 
     
     
         20 . 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 a gas X in the subject's lung, comprising program code for:
 a. Obtaining input of a series of logistically attainable end tidal partial pressure of gas X (PetX T ) for a respective interval;   b. Obtaining input of an amount of gas X required to be inspired by the subject in an inspired gas to target the PetX[i] T  for a respective interval; and   c. Controlling the amount in a volume of gas delivered to the subject in a respective interval to target the respective PetX[i] T  based on the input;   
       wherein at least one of the size and the number of intervals 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. 
     
     
         21 - 22 . (canceled) 
     
     
         23 . An apparatus as claimed in  claim 1 , wherein X is CO 2 . 
     
     
         24 . An apparatus as claimed in  claim 23 , wherein a series of PetCO 2  targets provide a series of controlled vasoactive stimuli for measurement of vascular reactivity. 
     
     
         25 . An apparatus as claimed in  claim 24 , wherein the series of PetCO 2  targets provide at least one of the following:
 a) a controlled vasoactive stimulus for measurement of cerebrovascular reactivity;   b) a controlled vasoactive stimulus for measurement of liver, kidney, heart or eye vascular reactivity; or   c) a simultaneous change the subject's end tidal partial pressures of oxygen and carbon dioxide to selected values, for example to potentiate a diagnosis or treat cancer; and   d) a controlled vasoactive stimulus for diagnosing steno-occlusive-disease.   
     
     
         26 . 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 (PetX T ), the method comprising:
 a. Obtaining input of a series of logistically attainable PetX T  values for a series of respective intervals comprising at least one of a set of PetX T  increments and set of PetX T  decrements; and   b. Determining an amount of gas X required to be inspired by the subject in an inspired gas to target the PetX T  for a respective interval;   c. Controlling a gas delivery device to deliver the amount of gas X in a volume of gas delivered to the subject in a respective interval to target the respective PetX T  for the interval.   
       wherein at least one of the size and the number of intervals 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. 
     
     
         27 - 29 . (canceled) 
     
     
         30 . A method as claimed in  claim 26 , wherein each interval is a respective breath [i] and wherein the 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[i 1 ] T  to PetX[i n ] 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. 
     
     
         31 . A method as claimed in  claim 26 , wherein the physiologic response over the time course of the response is exponential, and wherein the rate of change in PetX T  is selected such that two time constants in the progress of the response are achieved before a next interval. 
     
     
         32 . A method as claimed in any  claim 26 , wherein the physiologic response over the time course of the response is exponential, and wherein the rate of change in PetX T  is selected such that three time constants in the progress of the response are achieved before a next interval. 
     
     
         33 - 41 . (canceled) 
     
     
         42 . An apparatus as claimed in  claim 1 , wherein X is CO2. 
     
     
         43 . A method as claimed in  claim 42 , wherein a series of PetCO 2  targets provide a series of controlled vasoactive stimuli for measurement of vascular reactivity. 
     
     
         44 . A method as claimed in  claim 42 , wherein the series of PetCO 2  targets provide at least one of the following:
 a) a controlled vasoactive stimulus for measurement of cerebrovascular reactivity;   b) a controlled vasoactive stimulus for measurement of liver, kidney, heart or eye vascular reactivity; or   c) a simultaneous change the subject's end tidal partial pressures of oxygen and carbon dioxide to selected values, for example to potentiate a diagnosis or treat cancer; and   d) a controlled vasoactive stimulus for diagnosing steno-occlusive-disease.   
     
     
         45 - 79 . (canceled)