Reperfusion protection in resuscitation

Abstract

An apparatus and method for resuscitating a patient suffering from cardiac arrest or another condition in which normal circulation has been interrupted. A ventilator is used for delivering a gas mixture to the patient. The ventilator is configured to adjust the partial pressure of CO2 to one or more partial pressures high enough to slow expiration of CO2 from the patient's lungs and thereby maintain a reduced pH in the patient's tissues for a period of time following return of spontaneous circulation.

Claims

1. A system for assisting resuscitation of a patient, the system comprising: at least one processor and associated memory; and a ventilator configured to communicatively couple to the at least one processor, the at least one processor configured to: receive at least two measurements of a CO.sub.2 concentration in an airway of the patient, determine whether return of spontaneous circulation (ROSC) has occurred based on a comparison of the at least two measurements of the CO.sub.2 concentration in the airway of the patient, receive one or more input signals indicative of a concentration of CO.sub.2 in a tissue of the patient, process the one or more input signals indicative of the concentration of CO.sub.2 of the tissue of the patient to provide a measurement of the concentration of CO.sub.2 in the tissue of the patient, determine a CO.sub.2 partial pressure adjustment for an inspiratory gas mixture, based at least in part on the measurement of the concentration of CO.sub.2 in the tissue of the patient, to impact a pH of the tissue of the patient during a period of time following ROSC, generate an instruction indicative of the determined CO.sub.2 partial pressure adjustment, and provide the instruction to the ventilator, wherein the ventilator is configured to adjust a CO.sub.2 partial pressure in the inspiratory gas mixture based on the instruction.

2. The system of claim 1, wherein the at least one processor is communicatively coupled to at least one sensor configured to measure CO.sub.2 concentration in the airway of the patient and further wherein the at least one processor is further configured to receive from the at least one sensor the at least two measurements of the CO.sub.2 concentration in the airway of the patient.

3. The system of claim 1, wherein the at least one processor is further configured to determine, based on the one or more input signals indicative of the concentration of CO.sub.2 in the tissue of the patient, whether ROSC has occurred.

4. The system of claim 1, wherein the CO.sub.2 partial pressure adjustment impacts the pH of the patient's tissues for a predetermined period of time following ROSC.

5. The system of claim 1 further comprising at least one sensor and associated processing configured to determine the pH of the tissue of the patient.

6. The system of claim 5, wherein the at least one processor is further configured to determine the CO.sub.2 partial pressure adjustment based at least in part on the pH of the tissue of the patient.

7. The system of claim 5, wherein the CO.sub.2 partial pressure adjustment is effective to maintain the pH below 7.0 during the period of time following ROSC.

8. The system of claim 5, wherein the CO.sub.2 partial pressure adjustment is effective to maintain the pH at a constant level for a first portion of the period of time following ROSC.

9. The system of claim 8, wherein the CO.sub.2 partial pressure adjustment is effective to increase the pH at a first rate during a second portion of the period of time following ROSC, wherein the second portion of the period of time is subsequent to the first portion of the period of time.

10. The system of claim 9, wherein the first rate comprises no more than 0.4 pH units/minute.

11. The system of claim 9, wherein an absolute value of the pH at the end of the second portion of the period of time is no more than 6.8.

12. The system of claim 11, wherein the pH increases at a second rate during a third portion of the period of time, wherein the third portion of the period of time is subsequent to the second portion of the period of time.

13. The system of claim 12, wherein the CO.sub.2 partial pressure adjustment is effective such that, if the pH during the third portion of the period of time is less than 6.8, the second rate comprises approximately 0.4 pH units/minute or less; and, if the pH during the third portion of the period of time is greater than 7, the second rate comprises approximately 0.2 pH units/minutes or less.

14. The system of claim 12, wherein each of the first portion, the second portion, and the third portion of the period of time comprises up to approximately five minutes.

15. The system of claim 1, further comprising a display, wherein the at least one processor is configured to provide the instruction to the display.

16. The system of claim 1 further comprising valves configured to adjust the inspiratory gas mixture.

17. The system of claim 16 wherein the valves are further configured to add CO.sub.2 to the inspiratory gas mixture based on the determined CO.sub.2 partial pressure adjustment.

18. The system of claim 16 wherein the at least one processor is further configured to electronically control the valves at least in response to the determination that ROSC has occurred.

19. The system of claim 1 further comprising a user interface configured to capture input indicating that ROSC has occurred.

20. The system of claim 1 wherein the CO.sub.2 partial pressure adjustment comprises an change of a partial pressure of CO.sub.2 gas in the inspiratory mixture from a first partial pressure to one or more second partial pressures high enough to slow expiration of CO.sub.2 from the lungs of the patient and thereby maintain a reduced pH in the tissue of the patient, wherein the reduced pH is approximately at or below a pH level present in the tissue subsequent to an adverse cardiac event and immediately prior to ROSC.

Description

DESCRIPTION OF DRAWINGS

(1) FIG. 1 is the system block diagram of one implementation of one aspect of the invention, including a ventilator integrated with a mechanical chest compression device and a defibrillator.

(2) FIG. 2 is a block diagram of the ventilator if FIG. 1.

(3) FIGS. 3A and 3B are plots depicting a typical end-tidal capnographic measurement curve.

(4) FIGS. 4A and 4B are plots depicting the end-tidal capnographic curve (dotted line) with elevated levels of inspired CO.sub.2.

(5) FIG. 5 is a block diagram of a gas mixture control loop of the implementation of FIG. 1.

DETAILED DESCRIPTION

(6) There are a great many different implementations of the invention possible, too many to possibly describe herein. Some possible implementations that are presently preferred are described below. It cannot be emphasized too strongly, however, that these are descriptions of implementations of the invention, and not descriptions of the invention, which is not limited to the detailed implementations described in this section but is described in broader terms in the claims.

(7) Some implementations may reduce reperfusion injury by maintaining a low tissue pH during the time period immediately prior to and from 0-60 minutes subsequent to the return of spontaneous circulation (ROSC) by means of addition of carbon dioxide to the inspiratory gases while at the same time increasing oxygen content relative to normal room air concentrations to enhance oxygenation of the brain, heart and other vital organs.

(8) Referring to FIGS. 1 and 2, the block diagram in FIG. 1 shows an integrated resuscitation system (IRS) with components designed to address various aspects of a resuscitation: defibrillator 13, mechanical compressor 12, and ventilator 15. By control of the partial pressures of the ventilation gases (particularly oxygen), ambient air, and carbon dioxide via the mixing valves 35, the IRS can maintain a patient's tissue pH at approximately the below normal level present immediately prior to ROSC.

(9) The tissue pH is controlled by the following well known physiological mechanism. The transport of CO.sub.2 can have a significant impact on the acid-base status of the blood and tissues. The lung excretes over 10,000 molar equivalents of carbonic acid per day compared to less than 100 molar equivalent of fixed acids by the kidneys. Therefore, by altering alveolar ventilation and the elimination of CO.sub.2, the acidity of the tissues of the brain, heart, gut and other organs can be modified. CO.sub.2 is carried in the blood in three forms: dissolved, as bicarbonate, and in combination with proteins such as carbamino compounds. In solution, carbon dioxide hydrates to form carbonic acid:
CO.sub.2+H.sub.2OH.sub.2CO.sub.3

(10) The largest fraction of carbon dioxide in the blood is in the form of bicarbonate ion, which is formed by ionization of carbonic acid:
H.sub.2CO.sub.3H.sup.++HCO.sub.32H.sup.++CO.sub.3.sup.2

(11) Using the law of mass action, the Henderson-Hasselbalch equation is derived:
[H.sup.+]=K.sub.1[H.sub.2CO.sub.3]/[HCO.sub.3.sup.], or
[H+]=K(P.sub.CO2)/[HCO.sub.3.sup.],
where P.sub.CO2 is the total concentration of CO.sub.2 and H.sub.2CO.sub.3. The log form of the Hasselbalch equation takes the form:
pH=pK.sub.A+log(HCO.sub.3.sup.)/(0.03P.sub.CO2),
where K.sub.A is the dissociation constant of carbonic acid, equal to 6.1.

(12) Normal HCO.sub.3.sup. concentration is 24 mmol/liter, with a resultant pH of 7.4. During total ischemia induced by cardiac arrest or trauma, pH will fall to below 7, and commonly in the range of 6.5-6.8, as a result of increasing levels of CO.sub.2. At the resumption of circulation and gas exchange in the alveoli, the end-tidal carbon dioxide (E.sub.tCO.sub.2) value, as measured by the commonly used capnograph or capnometer, increases rapidly from a value typically below 10 mmHg found during arrest to a supranormal value of 50-75 mmHgnormal values are approximately 35 mmHgas the body attempts to reduce its CO.sub.2 levels.

(13) Referring to FIGS. 3A and 3B, phase I represents airway dead space. It is the CO.sub.2-free portion of the exhaled breath from the conducting airways. Phase II represents the mixing of airway dead space gas with alveolar gas and is characterized by a significant rise in CO.sub.2. Phase III represents alveolar volume. The plateau reflects the level of effective ventilation in the alveoli. Two lines are constructed on the graph; one on the slope of Phase III and the other such that areas p and q are equal.

(14) Airway dead space is measured from the start of expiration to the point where the vertical line crosses the exhaled volume axis. The volume of CO.sub.2 in the breath is equal to area X, the total area under the curve. Adding individual breath volumes allows minute CO.sub.2 elimination to be calculated in ml/min. Physiologic Vd/Vt as well as physiologic and alveolar dead space can also be calculated if arterial PCO.sub.2 is known. A line representing the arterial PCO.sub.2 value is constructed parallel to the exhaled volume axis creating areas Y and Z. Area X represents the volume of CO.sub.2 in the exhaled tidal volume. Areas Y and Z represent wasted ventilation due to alveolar and airway dead space respectively.

(15) Referring to FIGS. 1, 4A and 4B, and the flowchart in FIG. 5, the processing unit 14, made up of an electronic processor such as a microprocessor as well as memory and support logic, first determines that a cardiac arrest is in progress, by one or a combination of such known techniques as: (1) electrocardiographic (ECG) analysis to determine whether the ECG is a rhythm due to ventricular fibrillation, ventricular tachycardia, PEA or asystole or a rhythm of supraventricular origin such as a normal sinus rhythm; (2) analysis of the transthoracic impedance signal to determine whether there is blood flow; or (3) simply by means of an input via the user interface 6 by the rescuer 4 indicating that an arrest is in progress. If an arrest is determined to be in progress, the inspiratory gas mixture is adjusted via electronically-controlled flow valves 35 in the differential flow control (DFC) subunit to be predominantly oxygen (60-100%). Once in the CARDIAC ARREST state, the processing unit 14 will wait for input that defines ROSC. This input may be as simple as an input via the user interface by the rescuer that ROSC has occurred, though preferably the input includes a capnometric signal measuring end tidal CO.sub.2 (E.sub.tCO.sub.2) values 2 in the expired air. When the processing unit 14 detects an increase of more than 30% of the baseline cardiac arrest E.sub.tCO.sub.2 value in 30 seconds and a value greater than 25 mmHg, the processing unit 14 will enter the ROSC state, and begin the process of adding CO.sub.2 to the inspired gas mixture.

(16) In some implementations, the desired partial gas pressure of CO.sub.2 in the inspired gas mixture is solely a function of the E.sub.tCO.sub.2 value. The first ventilation will have the flow ratios of oxygen, room air and CO.sub.2 set such that the CO.sub.2 partial pressure (CO.sub.2i) is 90% of the E.sub.tCO.sub.2 value (CO.sub.2i.sup.L). The processing unit 14 then checks the E.sub.tCO.sub.2 value of the subsequent exhalation to verify that the end tidal value is higher than the CO.sub.2i; if so, the next CO.sub.2i is set to 110% of the most recent E.sub.tCO.sub.2. If the E.sub.tCO.sub.2 is not found to be higher than the CO.sub.2i, then the partial pressure of CO.sub.2 in the next ventilation is reduced by 10%. If, after three such cycles where the E.sub.tCO.sub.2 is not found to be higher than the CO.sub.2i, then the CO.sub.2i is reduced to zero to get a baseline level for expired CO.sub.2. If, on the ventilation cycle where the CO.sub.2i was set to 110% of the E.sub.tCO.sub.2 value (CO.sub.2i.sup.H), the E.sub.tCO.sub.2 value of the subsequent exhalation is not lower than the CO.sub.2i.sup.H then the partial pressure of CO.sub.2 for the next ventilation cycle will be increased a further 10%.

(17) Referring to FIG. 2, the ventilator provides for both negative and positive pressures by means of the double venturi 32 such as that described in U.S. Pat. No. 5,664,563. Safety mechanisms are provided by shutoff valve 31 and exhaust valve 28. Heater/humidifier element 33 conditions the gas prior to entering the inspiration circuit, and capnometric measurements are determined using the capnometric sensor 22 and tidal volume sensor 21.

(18) Referring again to FIGS. 3A and 3B, by measuring both flow rates and the CO.sub.2 concentration (partial pressure), the quantity of CO.sub.2 for the inspiration and expiration cycle can be tracked by integrating the CO.sub.2 flow. Though the amount of excess CO.sub.2 may be unknown, the amount of CO.sub.2 transferred from the bloodstream to the alveoli can be accurately controlled by measuring the difference in CO.sub.2 volume on the inspired and expired cycles. Thus to achieve constant CO.sub.2 levels, CO.sub.2i is increased to the level such that the volumes of CO.sub.2 on inspired and expired cycles are equal. Volumetric measurements for the inspired and expired cycles may be averaged over several cycles to increase accuracy.

(19) In other implementations, either the tissue CO.sub.2 or pH are measured by such methods as disclosed in U.S. Pat. No. 6,055,447, which describes a sublingual tissue CO.sub.2 sensor, or U.S. Pat. Nos. 5,813,403, 6,564,088, and 6,766,188, which describe a method and device for measuring tissue pH via near infrared spectroscopy (NIRS). NIRS technology allows the simultaneous measurement of tissue PO.sub.2, PCO.sub.2, and pH. One drawback of previous methods for the measurement of tissue pH is that the measurements provided excellent relative accuracy for a given baseline measurement performed in a series of measurements over the course of a resuscitation, but absolute accuracy was not as good, as a result of patient-specific offsets such as skin pigment. One of the benefits of the currently-described implementations is that they do not require absolute accuracy of these pH measurements, only that the offset and gain be stable over the course of the resuscitation. Because tissue pH responds slowly over the course of multiple ventilation cycles, it is used primarily to augment control of E.sub.tCO.sub.2 levels by adjusting CO.sub.2i with the goal of regulating tissue pH per the following regimen: (1) during the first 5 minutes following ROSC, the pH should remain flat; (2) during the time period of 5-10 minutes, the tissue pH should increase no more than 0.4 pH units/minute, and should be limited to not increase above an absolute number of 6.8; and (3) during the 10-15 minute time period, if the pH is still less than 6.8, CO.sub.2i is adjusted to allow pH to increase at a rate of approximately 0.4 pH units/minute, and if tissue pH is greater than 7 then CO.sub.2i is adjusted to a slower rate of 0.2 pH units/minute.

(20) In some cases, such as cardiac arrest cases with shorter periods of ischemia, it may be desirable to reduce pH levels below the levels present in the cardiac arrest victim by augmenting CO.sub.2 levels. In such cases, pH would be decreased during phase 1 of the regimen described in the previous paragraph.

(21) Tissue CO.sub.2, and thus pH, as well, are adjusted by increasing or decreasing inspired CO.sub.2 levels via the CO.sub.2i.sup.H and CO.sub.2i.sup.L levels; for instance, decreasing both levels will cause additional CO.sub.2 to be exhaled, thus reducing tissue pH. Adjustments are made in approximately 10% increments at approximately 3 times per minute. The low update rate of CO.sub.2i.sup.H and CO.sub.2i.sup.L levels is due to the fact that the time constant for pH changes due to CO.sub.2i changes is slow as well.

(22) In other implementations, medical knowledge such as that described in Crit Care Med 2000 Vol. 28, No. 11 (Suppl.) is incorporated into a closed loop feedback system to augment the methods described above for controlling tissue pH during resuscitation. As the author describes, the system of differential equations has been described in a number of publications. In this specific instance, the human circulation is represented by seven compliant chambers, connected by resistances through which blood may flow. The compliances correspond to the thoracic aorta, abdominal aorta, superior vena cava and right heart, abdominal and lower extremity veins, carotid arteries, and jugular veins. In addition, the chest compartment contains a pump representing the pulmonary vascular and left heart compliances. This pump may be configured to function either as a heart-like cardiac pump, in which applied pressure squeezes blood from the heart itself through the aortic valve, or as a global thoracic pressure pump, in which applied pressure squeezes blood from the pulmonary vascular bed, through the left heart, and into the periphery. Values for physiologic variables describing a textbook normal 70-kg man are used to specify compliances and resistances in the model. The distribution of vascular conductances (1/resistances) into cranial, thoracic, and caudal components reflects textbook distributions of cardiac output to various body regions. In addition to these equations, implementations may incorporate inspiratory volumetric measurement and the universal alveolar airway equation, the Henderson-Hasselbalch equation, and a three-compartment model of carbon dioxide storage in the body. The compartment with the lowest time constant corresponds to the well-perfused organs of brain, blood, kidneys, heart; the second compartment corresponds to skeletal muscle; and the third compartment corresponds to all other tissue.

(23) Referring to FIG. 5, a closed loop feedback method is employed, using state space methods with the system estimation block 55 provided by a physiological model as described above with augmentations to include CO.sub.2 and pH effects. The Feedback Controller 53 may employ such traditional control system methods as proportional, difference, integral (PID) or state feedback control methods, known to those skilled in the art.

(24) Since the cardiac arrest victim is spontaneously breathing during ROSC, and the central chemoreceptors will be stimulated by the elevated CO.sub.2 levels and depressed pH, it is necessary for the ventilator to respond to the victim's own inspiratory efforts. Pressure sensing is used to determine patient respiratory effort. A combination of synchronized intermittent mandatory ventilation (SIMV) and inspiratory pressure support ventilation (PSV) are used to provide proper responsiveness to victim respiratory needs while at the same time providing a sufficient amount of minute ventilation so that pCO.sub.2 can be regulated via CO.sub.2i. SIMV allows the victim to take breaths between artificial breaths and PSV assists the victim in making an inspiration of a pattern that is largely of their own control. With PSV, the amount of support is variable, with more support being provided in the early stages of ROSC and the support gradually reduced as the victim's status improves during the course of ROSC.

(25) The drug infuser 14 may be used to deliver other agents such as glutamate, aspartate or other metabolically active agents that may be particularly effective during the pH-depressed reperfusion state of the invention in renormalizing lactate levels and generating the ATP stores necessary to restore cytosolic calcium homeostasis prior to allowing pH to increase.

(26) The chest compressor 12 and ventilator 15 may be physically separate from the defibrillator, and the physiological monitor 10 and control of the chest compressor 12 and ventilator 15 may be accomplished by a communications link 16. The communications link 16 may take the form of a cable connecting the devices but preferably the link 16 is via a wireless protocol such as Bluetooth or a wireless network protocol such as Institute of Electrical and Electronics Engineers (IEEE) 802.11. The separate chest compressor 12 can be a portable chest compression device such as that commercially available as the Autopulse, provided by ZOLL Circulatory Systems of Sunnyvale, Calif. The separate ventilator 15 can be a ventilator such as that is commercially available as the iVent, provided by Versamed of Pearl River, N.Y. The separate drug infuser 14 can be a drug infusion device such as that commercially available as the Power Infuser, provided by Infusion Dynamics of Plymouth Meeting, Pa., or the Colleague CX, provided by Baxter Healthcare Corp., of Round Lake, Ill. The chest compressor 12, ventilator 15, drug infuser 14 and defibrillator 13 can also be integrated into one housing such as that for the Autopulse, provided by ZOLL Circulatory Systems of Sunnyvale, Calif.

(27) In other implementations, control and coordination for the overall resuscitation event and the delivery of the various therapies may be accomplished by a device 17 or processing element external to either the chest compressor, ventilator, or defibrillator. For instance the device 17 may be a laptop computer or other handheld computer or a dedicated computing device that will download and process the ECG data from the defibrillator, analyze the ECG signals, perform the determinations based on the analysis, and control the other therapeutic devices, including the defibrillator 13. While the system has been described for cardiac arrest, it is also applicable for trauma victims or other forms of arrest where the victim is suffering, from amongst other conditions, a global ischemia, and resuscitation from which requires the patient to transition through a state of reperfusion.

(28) Many other implementations of the invention other than those described above are within the invention, which is defined by the following claims. References to processing in the claims include a microprocessor (and associated memory and hardware) executing software.