Non-invasive determination of cardiac output, gas exchange and arterial blood gas concentration

[0001] The present invention is directed to the field of blood gas monitoring, specifically the non-invasive monitoring of arterial blood gas concentration.

[0002] Percutaneous oxygenators have been described in the prior art for more than twenty years. As disclosed in U.S. Pat. No. 4,911,689 to Hattler, a percutaneous oxygenator comprises a number of hollow, gas-permeable fibers. This device is inserted through a single small incision into a patient's venous system. When an oxygen supply is attached to the device, oxygen flows through the hollow fibers and diffuses through the wall of the fibers into the patient's blood. Conversely, carbon dioxide from the blood diffuses back across the fiber wall, up the fibers and out of the system to the atmosphere. While improvements to this design have been made, to date, no percutaneous oxygenator is able to fully provide the necessary oxygenation required. At best performance, prior art oxygenators may supply 50%-70% of required metabolic oxygen. Therefore, it has been proposed that percutaneous oxygenators may be used to augment natural patient respiration or mechanical ventilation support already provided to the patient through the patient's airway. The augmentation of the natural patient respiration may allow a patient to avoid mechanical ventilation. For a patient who is already receiving mechanical ventilation support, the introduction of percutaneous oxygenator support would reduce the demand for aggressive ventilatory treatment. This is desirable due to the fact that aggressive ventilatory treatment may cause lung injury or increase the cardiac stresses on the patient.

[0003] Percutaneous oxygenator technology is not limited in scope to merely the delivery of supplemental oxygen. The same catheterization technique of the patient with gas-permeable membrane fibers can be used to deliver a variety of medical gases intravenously into the patient's blood stream. This technique may be used to deliver anesthetic agent, or other medical gases such as carbon dioxide (CO₂), nitrogen (N), nitrous oxide (NO), or helium (He).

[0004] Typically, when a patient is receiving ventilatory support, the effectiveness of this support is monitored using a spirometer and respiratory gas monitor such as the Datex-Ohmeda S5 Gas Analyzer. The data collected from the spirometer and gas monitor is used to monitor the composition, flow rates, and exchange rates of the gases inspired and expired by the patient. However, patients receiving mechanical ventilatory support often have compromised gas exchange in their lungs. A patient receiving supplemental percutaneous oxygenator support often results in the erroneous prediction or estimation of the patient's blood gas concentration due to mismatched blood-gas exchange and compromised gas diffusion across the alveoli. Solutions to this problem have been invasive and time-consuming. Typically, blood samples must be drawn intermittently and individually analyzed to assess the patient's actual blood gas concentration and evaluate the adequacy of the combined treatment. While systems have been developed to automatically sample and analyze the patient's blood gas concentration, such as that disclosed in U.S. Pat. No. 4,516,580 to Polanyi, these systems require the invasive arterial insertion of a costly multi-parameter, multi-sensor transducer.

[0005] Despite improvements, all of the aforementioned systems are limited in their ability to continuously monitor a patient's blood gas concentration. All of these systems and methods require the taking of an actual blood sample. This inherently reduces the sampling rate of the patient's blood and additional time is required to compute the blood gas concentration. These delays produce a lag time that can inaccurately display the patient's blood gas concentration.

[0006] It is therefore desirable for a system by which the blood gas concentration of a patient receiving both mechanical ventilation and percutaneous oxygenator support may be determined without the introduction of an invasive intravascular transducer. It is also desirable for a system by which components already used in conjunction with or associated with the mechanical ventilation and/or percutaneous oxygenation of a patient are used to determine patient blood gas concentration.

[0007] An embodiment of the present invention is a system that comprises exchange catheter gas composition data, such as the composition and flow rates in and out of a percutaneous oxygenator to determine patient venous blood gas concentration resulting in continuous computation of patient arterial blood gas concentration.

[0008] In a further embodiment of the present invention, the exchange catheter gas composition data combines with pre-existing gas analysis data from the mechanical ventilation system comprising gas analyzer and spirometry data to continuously compute cardiac output trending, blood gas exchange analysis, and arterial gas concentrations.

[0009] It is a further aspect of the present invention that the present invention provides a continuous and noninvasive solution to the computation of arterial blood gas concentration.

[0012] FIG. 1 depicts a schematic diagram of a patient receiving both mechanical ventilation as well as percutaneous oxygenator support. The patient 10 receives mechanical ventilation support from a ventilator 12 via a patient interface 14 such as a face mask or endotracheal tube. The patient's mechanical ventilation support is augmented by a percutaneous oxygenator 16 which introduces an additional supply of oxygen to the patient venous blood via a gas exchange catheter 18 which is inserted into the patient's superior or inferior vena cava.

[0013] In a typical clinical setting where a patient is undergoing mechanical ventilation support the ventilator 12 is used in conjunction with a spirometer 20 and a gas analyzer 22 which receive samples of the gas inspired and expired by the patient 10 via a gas sampling tube 24. Alternatively, mainstream gas analyzers that measure gas concentration directly from the patient gas stream without having the gases sampled via a tube may also be used. The spirometer 20 monitors the volume and flow rate of the air that is inspired and expired by the patient. The gas analyzer 22 derives the concentrations of the different component gases breathed by the patient 10.

[0014] Referring back to the present invention as depicted in FIG. 1, a CPU 26 collects data from a variety of sources including the ventilator 12, percutaneous oxygenator 16, the spirometer 20, and the gas analyzer 22. Then the CPU processes this data through a series of algorithms 28 by which the patient's blood gas concentration 30 is derived.

[0015] The present invention will be described in consideration of the exchange of oxygen to the venous blood stream and the related computation of the oxygen exchange and arterial oxygen concentration. However, it is understood that a similar device arrangement and method can be used to compute other gas exchanges and arterial concentrations, such as carbon dioxide (CO₂), nitrogen (N), nitrous oxide (NO), helium (He), carbon monoxide (CO), or anesthetic gases. As previously stated, the CPU 26 receives data relating to the patient's blood gas concentration from a variety of sources connected to the patient. As the ventilator provides inspiratory support to the patient 14, the concentration of inspired oxygen 32 is provided to CPU 26. The spirometer 20 provides data to the CPU 26 representing the inspiratory flow rate 34 and the expiratory flow rate 36. The gas analyzer 22 provides CPU 26 with data representative of the concentration of expired oxygen 38 of the patient 10.

[0016] As additional oxygen support is provided to the patient by the percutaneous oxygenator 16, the individual flow rates of the component gases entering the catheter 18 are known either by the manual control settings of the gases by the clinician or by the measurement of the gas concentration and flow rate by a separate component downstream (not pictured). The gas concentration and flow rate data, namely the concentration of oxygen going into the catheter 40 and the flow rate of oxygen into the catheter 42 are sent to CPU 26. As gases exit the distal end of the catheter 18, the concentration of the component gases are determined by a second gas analyzer 44 that provides data representative of the concentration of oxygen 46 coming out of the catheter 18 to CPU 26. The total flow of the gases out of the catheter 18 is measured by a flow sensor 48 and is provided to the CPU 26 as the total flow out of the catheter 50.

[0017] The CPU 26 uses the data that it has received, as described above, with a variety of algorithms to be herein described further. By using the law of conservation of mass, the gas exchange and arterial oxygen concentration can be computed as herein described. Included Table I is a summary of the variables used in the following equations, a description of the variable, the source of this value, and an associated reference number if applicable.

[0018]

TABLE I
			Ref.
Variables	Description	Source	#
Vh	Effective gas exchange volume	Calculated (Eq. 1)	—
	of the intravenous gas
	exchange catheter
CO2out	Concentration of O2 out of the	Gas Analyzer (44)	46
	catheter
FO2in	Flow of O2 into the catheter	P.O. (16)	42
Ftot—out	Total Flow out of the catheter	Flow Sensor (48)	50
Keff	Gas equilibration coefficient	Constant/Known	—
CvenousO2	Concentration of venous O2	Calculated (Eq. 2)	—
CO	Average Cardiac Output	Calculated (Eq. 3)	—
CartO2	Average Concentration of	Calculated (Eq. 7)	30
	arterial O2
CinspO2	Concentration of inspired O2	Ventilator (12)	32
Finsp	Flow of inspired gases	Spirometer (20)	34
CexpO2	Concentration of expired O2	Gas Analyzer (22)	38
CO2in	Concentration of O2 into the	P.O. (16)	40
	catheter
CreturnO2	Concentration of venous	Calculated (Eq. 6)	—
	return O2
Fexp	Flow of expired gases	Spirometer (20)	36

[0019] By definition, the mixed venous concentration of oxygen entering the right atria can be computed using the gas equilibration coefficient, K_eff, which is known to the system by the design or calibration of the percutaneous oxygenator 16,

[0020] $\begin{array}{cc}{V}_h*\frac{d\left(C_{O_2\mathrm{out}}\right)}{dt}=F_{O_{2}in}-\left[C_{O_2\mathrm{out}}*F_{\mathrm{tot\_out}}\right]-K_{\mathrm{eff}}*\left[C_{O_2\mathrm{out}}-C_{{\mathrm{venous}O}_2}\right]& \left(\mathrm{Eq}.1\right)\end{array}$

[0021] At steady state and in the catheter flow condition labeled as _—1, the derivative of C_O2out—1 with respect to time, tends to zero, giving the steady state concentration of the venous blood to the right atria to be:
C_venousO2—1=(C_O2out—1−F_tot—out)−F_O2in—1+K_eff*C_O2out  (Eq. 2)

[0022] Now considering the gas exchange in the lungs, by integrating over a breath, the arterial oxygen concentration can be found by solving the following integral equation:

[0023] $\begin{array}{cc}\int \left(\mathrm{CO}*C_{{\mathrm{arto}}_2}\right)dt=\int \left(\mathrm{CO}*C_{{\mathrm{venousO}}_{2\_1}}+C_{{\mathrm{inspO}}_2}*F_{\mathrm{insp}}-C_{{\mathrm{expO}}_2}*F_{\exp }\right)dt& \left(\mathrm{Eq}.3\right)\end{array}$
Where CO is the cardiac output and can be found by using two different settings of C_O2in 42 or F_O2in 40.

[0024] Now assuming that the concentration of O2 in the catheter is being altered from a condition_—1 to condition_—2, and set in a duration that is much shorter than the recirculation time of blood, but is sufficiently long for a steady state to settle, the uptake of O2 surrounding the compartment around the catheter 18 and the vena cava at a steady state in the two conditions are described by the two gas mass balance equations,

[0025] $\begin{array}{cc}\int \left(F_{o_2\mathrm{in}\_1}-\left(C_{O_{2\_\mathrm{out}\_1}}*F_{\mathrm{tot\_out}\_1}\right)\right)dt=\int \left(\mathrm{CO}*\left(C_{{\mathrm{returno}}_2}-C_{{\mathrm{venousO}}_{2\_1}}\right)\right)dt& \left(\mathrm{Eq}.4\right)\\ \int \left(F_{o_2\mathrm{in}\_2}-\left(C_{O_{2\_\mathrm{out}\_2}}*F_{\mathrm{tot\_out}\_2}\right)\right)dt=\int \left(\mathrm{CO}*\left(C_{{\mathrm{returno}}_2}-C_{{\mathrm{venousO}}_{2\_2}}\right)\right)dt& \left(\mathrm{Eq}.5\right)\end{array}$
Where the indices _—1 and _—2 indicate the settings or measurements under condition_—1 and condition_—2, respectively, of the oxygen concentration into the catheter 18. C_returnO2 is the flow averaged concentration of mixed venous blood in the superior or inferior vena cava and remains constant during the two settings of O2 concentration into the catheter. Furthermore, assuming that the gas flow and concentration into the catheter 18, C_returnO2 and cardiac output (CO) are constant over the two integral period, the integral expression may be removed from the integration and multiplied by the duration and can be divided out from both sides of the equations.

[0026] By subtracting the equation in condition_—1 from the equation in condition_—2, the unknown variable C_returnO2 is eliminated and after rearranging the resulting equation, the cardiac output is obtained:

[0027] $\begin{array}{cc}\mathrm{CO}=\frac{\begin{array}{c}(\left(F_{O_2\mathrm{in\_}1}-\left(C_{O_2\mathrm{out\_}1}*F_{\mathrm{tot\_out}\_1}\right)\right)-\\ \left(\left(F_{O_2\mathrm{in\_}2}-\left(C_{O_2\mathrm{out\_}2}*F_{\mathrm{tot\_out}\_2}\right)\right)\right)\end{array}}{\left(C_{\mathrm{venous}{O}_2\_2}-C_{\mathrm{venous}{O}_2\_1}\right)}& \left(\mathrm{Eq}.6\right)\end{array}$

[0028] By substituting the cardiac output calculated in Equation 6 back into the arterial blood gas equation, with C_venousO2 computed from Equation 2, solving Equation 3 yields the concentration of arterial oxygen 30, as shown in Equation 7.

[0029] $\begin{array}{cc}{C}_{\mathrm{art}{O}_2}=\frac{\frac{\int (\mathrm{CO}*C_{\mathrm{venous}{O}_2\_1}+C_{\mathrm{insp}{O}_2}*}{F_{\mathrm{insp}}-C_{\exp O_2}*F_{\exp })dt}}{\int \left(\mathrm{CO}\right)dt}& \left(\mathrm{Eq}.7\right)\end{array}$

[0030] The arterial concentration of CO2, C_artCO2, can be derived by perturbing the inflow of gases, F_O2in, and solving a set of similarly derived equations except for the substitution of CO2 concentrations, such as C_CO2out and C_venousCO2, for the corresponding O2 concentrations.

[0031] In an embodiment of the present invention, the CPU 26 further uses the derived patient blood gas concentrations 30 to control the operation of the percutaneous oxygenator 16 or the ventilator 12. For example, if the patient's blood gas concentration of oxygen becomes too low, the CPU may automatically adjust the oxygen concentration or the flow rate of oxygen supplied to the patient 10 by the percutaneous oxygenator 16. It is also understood that the operational controls of the ventilator 12 may be adjusted to raise the oxygen concentration in the patient's blood. The CPU 26 may adjust the respiratory rate, respiratory pressure, positive end expiratory pressure (PEEP), or the concentration of supplemental oxygen supplied by the ventilator 12. It is under stood that this automated control may be used in the control of other gases supplied to the patient as herein described. Furthermore, it is understood that in an embodiment of the present invention, CPU 26 may signal or alarm a clinician to initiate changes in the operational parameters of the percutaneous oxygenator 16 or ventilator 12 instead of automatedly performing these functions.

[0032] The advantage of this invention is that the oxygen and carbon dioxide gas exchange, and the arterial concentrations of oxygen and carbon dioxide can be computed continuously and trended without an additional arterial blood gas monitor. This reduces the cost of assessing the progression of a gas exchange therapy and replaces the time consuming and slow responding laboratory blood gas sample analysis. Therefore, the present invention provides an accurate, non-invasive approach to continuously monitoring arterial oxygenation levels of a patient receiving both mechanical ventilatory support and percutaneous oxygenation support.

[0033] This written description uses examples to disclose the invention, including the best mode, and also to enable any person skilled in the art to make and use the invention. The patentable scope of the invention is defined by the claims and may include other examples that occur to those skilled in the art. Such other examples are intended to be within the scope of the claims if they have structural elements that do not differ from the literal language of the claims, or if they include equivalent structural elements of insubstantial difference from the literal language of the claims.

[0034] Various alternatives and embodiments are contemplated as being with in the scope of the following claims, particularly pointing out and distinctly claiming the subject matter regarded as the invention.