System and method for safely delivering an efficient amount of oxygen to needed organs during cardiopulmonary resuscitation

Abstract

A system for safely delivering an efficient amount of oxygen to vital organs during cardiopulmonary resuscitation (CPR) is described, and respective methods and endotracheal devices for performing semi-voluntary positive pressure ventilation are further described, the system being comprised of at least one limb compression device, a positive pressure ventilation system, an endotracheal tube, a cardiac stimulation device, an endotracheal pressure sensor, and a synchronizer, and the method being comprised of compressing at least one limb device to occlude blood flow to the limb, delivering a mixed gas, providing an endotracheal tube, applying a deployed configuration, applying a hold configuration, running the cardiac stimulation device, determining pressure, and synchronizing timing. The endotracheal device is comprised of an elongated tube, and a sealing cuff that assumes a deployed configuration and a hold configuration.

Description

Detailed Description of the Invention

[0001] (Technical field) The present invention relates generally to the fields of emergency medicine and cardiology, and more specifically to means for improving the meaningful outcome of cardiac arrest.

[0002] (Introduction) Cardiac arrest is the cause of over 500,000 deaths each year in the United States and millions worldwide. The cause of cardiac arrest in the majority of patients is a critical narrowing or blockage of a coronary artery, leading to the cessation of the heart's pumping function. As a result, blood flow stops suddenly and oxygen delivery to tissues ceases. The consequences are devastating. While some tissues (e.g., skin, fat, and muscle) have stores of oxygen and high-energy compounds that allow them to survive for several hours without irreversible damage, other tissues (e.g., myocardium and brain) do not have such stores and require a continuous high oxygen supply, and therefore cannot tolerate brief periods of ischemia without irreversible damage and injury to their cells.

[0003] The current American Heart Association (AHA) protocol for survival after cardiac arrest is to perform cardiopulmonary resuscitation (CPR), i.e. chest compressions and electrical defibrillation, to restore mechanical and electrical cardiac function, also known as return of spontaneous circulation (ROSC).

[0004] The key to jump-starting such an arrested heart is to rapidly restore blood flow to the myocardium through the coronary arteries. However, today it is clearly understood that ROSC alone is not enough, and that to ensure meaningful survival after cardiac arrest, it is important to avoid neurological damage during cardiopulmonary resuscitation (CPR). That is, blood flow and oxygen supply to the brain must be maintained during CPR. Unfortunately, the overall clinical experience with CPR more than 60 years after chest compressions were first introduced is very disappointing. In a recent study, CPR was performed on 8000 patients who witnessed cardiac arrest outside of hospital. Half of them received intravenous epinephrine (Epi), and the other half received the same CPR protocol but without epinephrine. The Epi group had a much higher ROSC on arrival at the hospital than the patients who did not receive Epi. However, when comparing neurologically intact survival 30 days after cardiac arrest, no statistically significant difference was found between the two groups.

[0005] Thus, it is clear that although the use of Epi is beneficial in terms of reviving the heartbeat, its use does not help, and perhaps even harm, brain viability. Similar results have been shown in multiple clinical and experimental studies. The flow diagram in Figure 1 illustrates the sequence of physiological events that occur during cardiac arrest and CPR. Clearly, better measures are needed to improve the meaningful outcomes of CPR.

[0006] Analysis of current practices and mechanisms during CPR that contribute to poor neurological outcomes. Administration of Epi and other vascular compression drugs constricts arteries, including those in the brain, resulting in increased resistance to blood flow. This may increase blood pressure, but it also clearly impedes blood flow and inhibits oxygen transport to brain tissue.

[0007] (a) The physiological mechanism of "reactive hyperemia," also known as hypoxic vasodilation, causes maximal dilation of arterioles throughout the body. Therefore, when Epi or other vasopressor drugs are injected into a vein, they travel slowly through the wide open arteries. Therefore, the timing of the arrival of intravenously injected Epi or other vasopressor drugs at the tissues of the body is highly heterogeneous during CPR. Tissues close to the heart, such as the brain, receive the drug first, while more distant tissues, such as the legs, receive the drug much later. As a result, the cerebral circulation contracts earlier than the peripheral circulation. Due to the nature of simple fluid mechanics, blood flow generated by chest compression CPR is preferentially diverted to the wide open periphery, while flow into the constricted cerebral arteries is prevented. Epi reaches the periphery later. However, due to its short half-life of 4 minutes and the slow blood flow caused by CPR, it is already partially inactivated by the time it reaches the periphery. This paradoxical "steal phenomenon" deprives brain tissue of vital oxygen transport to cells.

[0008] If the patient is not breathing, positive pressure ventilation is of course necessary. (a) Too much ventilation compared to the greatly reduced metabolic production of CO2 during CPR causes a fall in arterial PCO2 (PaCO2). Low PaCO2 is a strong cause of cerebral vasoconstriction, again impairing cerebral blood flow. (b) Low PaCO2 causes a shift to the left of the oxygen-hemoglobin dissociation curve (Bohr effect). This shift leads to stronger binding of oxygen to hemoglobin and less offloading of oxygen molecules in the tissues. As a result, for every ml of blood flowing through the capillaries, significantly less oxygen is delivered (e.g., 20-35% less), whatever the level of capillary PO2. Any attempt by the tissues to extract more oxygen from the blood is futile, since the PO2 at the capillary end must be lowered, thereby reducing the diffusion driving force that transports oxygen molecules from the capillaries to the mitochondria. The obstructed flow, reduced oxygen delivery, and smaller partial pressure gradient critically limit oxygen transport to the brain. It has been confirmed in several animal and clinical studies that hyperventilation must be avoided during CPR. (c) Positive pressure ventilation with relatively large tidal volumes increases intrathoracic pressure, expands the alveoli, thereby preventing venous blood return to the right side of the heart, compresses the pulmonary capillaries, increasing their resistance to flow, and stretches (elongates) the pulmonary capillaries, also increasing their resistance to flow. These phenomena cause the cardiac chambers to fill up and, even as they are compressed, only a small amount of blood is expelled with each compression. It should be noted that attempts to counter these effects of positive pressure ventilation by maintaining the reduction in chest volume with chest compressions by preventing air from entering the airways (e.g., with "impedance threshold devices") and by applying negative pressure to the airways by using chest wall compression-decompression (suction) forces during CPR are of limited effectiveness due to the nature of the dynamic collapse of the central veins and pulmonary vessels, and of the distal, noncartilaginous airways of the lungs. Under certain circumstances, negative intrathoracic pressure on thoracic vessels and small airways can lead to vascular collapse, flow restriction, and flutter.

[0009] The fall in PaCO2 associated with relatively excessive ventilation, followed by an increase in pH ("respiratory alkalosis"), is an independent cause of a leftward shift in the O2-hemoglobin dissociation curve. This is further insulted by the long-standing but now discouraged intravenous administration of sodium bicarbonate to counteract metabolic acidosis, presumably caused by the production of lactic acid by anaerobic tissue metabolism. Administration of bicarbonate shifts the O2 dissociation curve further to the left, thereby limiting the transport of O2 molecules from the blood to the tissues.

[0010] The diagrams shown in the drawings give an overview of these mechanisms.

[0011] (background art) The use of vasodilators during CPR has previously been shown to be beneficial in multiple animal studies by significantly increasing cerebral blood flow. The compound previously used was intravenous administration of sodium nitroprusside (Na-Nitroprusside (SNP)), a known potent vasodilator. The animal studies also demonstrated that administration of SNP reduced systemic blood pressure, which would be expected if vasodilation was induced. A reduction in blood pressure is also known to occur when PaCO2 is elevated.

[0012] Attempts to counteract the extreme vasodilation described in 2 above using mechanical means have so far been largely unsuccessful, as outlined below.

[0013] Studies using Military (Medical) Antishock Pants (MAST), a garment with an inflatable bladder that covers the entire lower body, including the abdomen and legs, have shown no beneficial effects. There are three main reasons why this method failed.

[0014] The MAST does not inflate sequentially from distal to proximal, so there is no peripheral compression of blood. In fact, if the proximal bladder inflates before the distal bladder, the MAST may act as a venous tourniquet, trapping blood in the periphery rather than autotransfusing it.

[0015] MAST cannot be gradually removed: removal by either contracting the bladder or opening the Velcro® fastenings often results in a sudden opening of the peripheral vascular bed, leading to a rapid fall in peripheral resistance and a drop in blood pressure, often resulting in a re-disruption of the patient's homeostasis.

[0016] Pressure on the abdomen by the abdominal bladder displaces the viscera caudally and restricts expansion of the lower ribs, causing severe respiratory problems.

[0017] MAST takes too long to apply (>5 minutes). Researchers have attempted to increase peripheral resistance during CPR by tightly strapping the abdomen. Again, this method has failed to improve outcomes in CPR experiments in laboratory animals (pigs).

[0018] Leg elevation during CPR has been tried before, but only 45% of the blood is removed from the legs by leg elevation (Blond et al, Acta Ortho Scand. 2001). Furthermore, with each chest compression, blood is forced into the distended leg arteries, minimizing the benefit of leg elevation over the extra manpower required during transport.

[0019] Esmarch bandages were reported in 1951 by Dr Woolworth of Tasmania to have a beneficial effect in restretching the heart during open-chest cardiac massage in a child undergoing ether anaesthesia for orthopedic surgery and experiencing cardiac arrest. The child did not survive.

[0020] The application of tourniquets, such as traumatic hemostasis or pneumatic hemostasis, are known techniques that could theoretically increase vascular resistance and improve the effectiveness of cardiac massage by directing stroke volume to the necessary organs. However, as is well known in orthopedic surgery, stopping blood flow to an extremity without first completely emptying it of blood is often accompanied by intravascular coagulation. These clots can rapidly migrate to the lungs or brain upon release of hemostasis (Sulek 1999), resulting in pulmonary embolism or cerebral infarction.

[0021] Occlusion of the aorta with an inflated balloon inserted through the femoral artery is a heroic measure that has significant beneficial effects in experimental animals (Sesma et Al, Am.J. Emerg.Med.Effect of Intra-aortic occlusion balloon in external thoracic compressions during CPR in pigs - ScienceDirect), https: / / www.sciencedirect.com / science / article / abs / pii / S0735675702000402.

[0022] An important prior art is the use of Extracorporeal Membrane Oxygenators (ECMO) during CPR to attempt to supply oxygenated blood to vital organs (Speidl 2015 Extracorporeal membrane oxygenation in cardiac arrest). ECMO is often successful when used (meaning 4-54% survival), but is rarely used due to logistical challenges, team and equipment availability, and cost. In European metropolitan settings, it is only used in 1-2% of cardiac arrest patients. https: / / www.escardio.org / static-file / Escardio / Congresses / Congress management / Acute Cardiovascular Care / Documents / Slides_FP344.pdf. (Summary of the invention) The following summary of the invention is provided to provide a basic understanding of some principles underlying various aspects and features of the present invention. This summary is not an extensive overview of the invention, and as such it is not intended to specifically identify all key or critical elements of the invention, nor is it intended to delineate the scope of the invention. Its sole purpose is to present some concepts of the invention in a simplified form as a prelude to the more detailed description that follows.

[0023] The present invention has been made in view of the deficiencies of the prior art and provides systems, methods and processes to overcome these deficiencies. According to some embodiments and aspects of the present invention, a system for safely delivering an efficient amount of oxygen to vital organs during cardiopulmonary resuscitation (CPR) is provided. The system comprises at least one limb compression device configured to exert a distal to proximal sequential compression force on the limb to occlude blood flow to the limb, and a positive pressure ventilation system configured to deliver a mixed gas by positive pressure. According to some embodiments and aspects of the present invention, the positive pressure ventilation system comprises a carbon dioxide reservoir containing a carbon dioxide enriched gas, a molecular oxygen reservoir containing a molecular oxygen enriched gas, a controllable mixing module operably connected to the carbon dioxide reservoir and the molecular oxygen reservoir and configured to controllably mix the molecular oxygen enriched gas with the carbon dioxide enriched gas, and at least one carbon dioxide partial pressure sensor selected from the group consisting of:

[0024] an arterial blood carbon dioxide partial pressure sensor and an end-tidal carbon dioxide partial pressure sensor configured to detect carbon dioxide partial pressure in arterial blood; a controller operatively connected to the controllable mixing module and the at least one carbon dioxide partial pressure sensor, configured to control at least one ratio selected from the group consisting of: a ratio of molecular oxygen enriched gas and a ratio of carbon dioxide enriched gas in a mixture of molecular oxygen enriched gas and carbon dioxide enriched gas; an endotracheal tube including a sealing cuff disposed on a distal portion of the endotracheal tube, the endotracheal tube being configured to iteratively assume the following configurations: a deployed configuration in which the sealing cuff engages an inner surface of the trachea while maintaining an inflow of gas from the endotracheal tube into the trachea, and a non-deployed configuration in which the sealing cuff disengages from the inner surface of the trachea while maintaining a natural outflow of gas from the trachea.

[0025] According to some embodiments and aspects of the invention, the system comprises a cardiac stimulation device configured to restore spontaneous circulation of arterial blood by applying at least one stimulus selected from the group consisting of mechanical and electrical stimuli to the myocardium at predetermined time intervals, an intratracheal pressure sensor configured to continuously determine intratracheal pressure, and a synchronizer configured to time an injection phase of the positive pressure ventilation system with the start of a depressurization phase of the cardiac stimulation.

[0026] In some embodiments, sequential distal to proximal compressive forces on the limb are achieved by ascending contracting elastic rings.

[0027] In some embodiments, the sequential distal to proximal compressive force on the limb is achieved by applying at least one element selected from the group consisting of an elastic bandage, an elastic limb wrap with an adjustable closure, and an inflatable limb wrap with an adjustable closure.

[0028] In some embodiments, the at least one limb compression device is configured to occlude arterial inflow of blood to the limb by applying a surface skin pressure range selected from the group consisting of 100 mmHg and 200 mmHg, 200 mmHg and 300 mmHg.

[0029] In some embodiments, the gas mixture is selected from the group consisting of 95% molecular oxygen and 5% carbon dioxide, 0.1-2.0% carbon dioxide (remainder molecular oxygen), 2.1-4.0% carbon dioxide (remainder molecular oxygen), 4.1-5.6% carbon dioxide (remainder molecular oxygen), 0.1-5.0% carbon dioxide (remainder molecular oxygen), 30-50% molecular oxygen and the chemical element xenon, 0.1-5.0% carbon dioxide (remainder molecular oxygen) and the chemical element argon.

[0030] In some embodiments, the controllable mixing module controllably mixes a gas mixture of 5% carbon dioxide and 95% molecular oxygen with pure 100% molecular oxygen according to feedback from at least one carbon dioxide partial pressure sensor selected from the group consisting of an arterial blood carbon dioxide partial pressure sensor and an end-tidal carbon dioxide partial pressure sensor, to maintain an arterial blood carbon dioxide partial pressure level between 41 and 45 mmHg.

[0031] In some embodiments, the controllable mixing module controllably mixes a hydrocarbon gas of 5% carbon dioxide and 95% molecular oxygen with pure 100% molecular oxygen according to feedback from at least one carbon dioxide partial pressure sensor selected from the group consisting of: an arterial blood carbon dioxide partial pressure sensor, and an end-tidal carbon dioxide partial pressure sensor, and maintains an arterial blood carbon dioxide partial pressure level in at least one pressure range selected from the group consisting of: 41-45 mmHg, 46-50 mmHg, 51-55 mmHg, 56-65 mmHg according to feedback from at least one carbon dioxide partial pressure sensor selected from the group consisting of an arterial blood carbon dioxide partial pressure sensor and an end-tidal carbon dioxide partial pressure sensor.

[0032] In some embodiments, the controllable mixing module controllably mixes a gas mixture of 5% carbon dioxide, 30% molecular oxygen, and 65% chemical element xenon with a gas mixture of 30% molecular oxygen and 70% chemical element xenon according to feedback from at least one carbon dioxide partial pressure sensor selected from the group consisting of an arterial blood carbon dioxide partial pressure sensor and an end-tidal carbon dioxide partial pressure sensor to maintain an arterial blood carbon dioxide partial pressure level between 41 and 65 mmHg.

[0033] In some embodiments, the controllable mixing module controllably mixes a gas mixture of 5% carbon dioxide, 50% molecular oxygen, and 45% chemical element xenon with a gas mixture of 5% carbon dioxide, 50% molecular oxygen, and 50% chemical element xenon according to feedback from at least one carbon dioxide partial pressure sensor selected from the group consisting of an arterial blood carbon dioxide partial pressure sensor and an end-tidal carbon dioxide partial pressure sensor to maintain an arterial blood carbon dioxide partial pressure level between 41 and 65 mmHg.

[0034] In some embodiments, the controllable mixing module controllably mixes a gas mixture of 5% carbon dioxide, 30% molecular oxygen and 65% chemical elemental argon with a gas mixture of 30% molecular oxygen and 70% chemical elemental argon according to feedback from at least one carbon dioxide partial pressure sensor selected from the group consisting of an arterial blood carbon dioxide partial pressure sensor and an end-tidal carbon dioxide partial pressure sensor to maintain an arterial blood carbon dioxide partial pressure level between 41 and 65 mmHg.

[0035] In some embodiments, the controllable mixing module controllably mixes a gas mixture of 5% carbon dioxide, 50% molecular oxygen and 45% chemical elemental argon with a gas mixture of 5% carbon dioxide, 50% molecular oxygen and 45% chemical elemental argon according to feedback from at least one carbon dioxide partial pressure sensor selected from the group consisting of an arterial blood carbon dioxide partial pressure sensor and an end-tidal carbon dioxide partial pressure sensor to maintain an arterial blood carbon dioxide partial pressure level between 41 and 65 mmHg.

[0036] According to some embodiments and aspects of the present invention, there is provided a method of safely delivering an efficient amount of oxygen to vital organs during cardiopulmonary resuscitation (CPR), comprising compressing at least one limb device to occlude blood flow to the limb by applying sequential distal to proximal compression forces to the limb, and delivering a mixed gas by positive pressure ventilation, the delivering including the steps of supplying a carbon dioxide enriched gas, supplying a molecular oxygen enriched gas, controllably mixing the molecular oxygen enriched gas and the carbon dioxide enriched gas, detecting the partial pressure of carbon dioxide in arterial blood, and controlling at least one ratio selected from the group consisting of a ratio of the molecular oxygen enriched gas and a ratio of the carbon dioxide enriched gas in the mixture of the molecular oxygen enriched gas and the carbon dioxide enriched gas.

[0037] According to some embodiments and aspects of the invention, the method includes providing an endotracheal tube including a sealing cuff disposed on a distal portion of the endotracheal tube; applying a deployed configuration to the sealing cuff in which the sealing cuff engages an inner surface of the trachea while maintaining an inflow of gas from the endotracheal tube into the trachea; applying a retained configuration to the sealing cuff in which the sealing cuff disengages from the inner surface of the trachea while maintaining a natural outflow of gas from the trachea; running a myocardial stimulation device by applying at least one stimulus selected from the group consisting of mechanical and electrical stimuli to the myocardium at predetermined time intervals to return natural circulation of arterial blood; and continuously measuring pressure in the trachea and synchronizing the start of an injection phase of the positive pressure ventilation system with a decompression phase of the cardiac stimulation.

[0038] According to some embodiments and aspects of the invention, there is provided an endotracheal device for semi-voluntary positive pressure ventilation, the endotracheal device including an elongate tube configured for endotracheal deployment and a sealing cuff disposed on a distal portion of the elongate tube, the sealing cuff configured to repeatedly assume a deployed configuration and an indwelling configuration, in which the sealing cuff is unfolded to engage an inner surface of the trachea while maintaining an inflow of gas from the endotracheal tube into the trachea, and in which the sealing cuff is folded to disengage from the inner surface of the trachea while maintaining a natural outflow of gas from the trachea,

[0039] In some embodiments, the sealing cuff comprises an inflatable toroidal structure that includes an inflatable lumen.

[0040] In some embodiments, the intratracheal device for providing semi-voluntary positive pressure ventilation further comprises at least one conduit connecting an inflatable lumen of the sealing cuff and a lumen of the elongate tube.

[0041] In some embodiments, the intratracheal device for semi-voluntary positive pressure ventilation further comprises at least one outlet in a forward distal portion of the toroidal structure of the sealing cuff configured to maintain flow of gas from the inflatable lumen of the sealing cuff into the trachea.

[0042] In some embodiments, the elongate tube includes a one-way flow check valve configured to maintain the flow of gas from the endotracheal tube to the trachea.

[0043] The present invention discloses prescribing a target hyperventilatory (i.e., above normal) level of PaCO2, either by directly measuring the PCO2 in arterial blood (PaCO2) or by monitoring the CO2 fraction at the end of expiration (also known as end-tidal PCO2 (PETCO2)), and using the PaCO2 as feedback information to vary the ratio of two gas mixtures, one containing 5% or 5.6% CO2 and oxygen, and optionally a neuroprotective inert gas such as xenon or argon, and the other containing the same composition but without CO2. The mixer can increase or decrease the percentage of CO2 in the mixture, depending on the instantaneous level of PaCO2 (or PETCO2). The PaCO2 for a given hyperventilatory level is typically between 41 mmHg and 60 mmHg, more commonly between 46 mmHg and 55 mmHg. These PaCO2 levels are known to cause (a) vasodilation, (b) a shift to the right of the O2-hemoglobin dissociation curve, and (c) stimulation of respiratory activity if the patient is able to return to spontaneous breathing.

[0044] Thus, to counteract the systemic vasodilation caused by administering CO2-enriched gas to raise PaCO2, the present invention prescribes the simultaneous use of means to constrict peripheral, particularly extremity, blood vessels. Thus, the present invention discloses the application of sequential distal-to-proximal limb compression devices that squeeze blood out of the limbs into the central circulation and block blood from re-entering the limb. Such devices include, but are not limited to, elastic contraction rings, elastic contraction rings with contracting elastic sleeves (stockinettes), manual elastic wraps, manual elastic bandages, and sequentially inflatable pneumatic contraction wraps, as shown in the drawings and detailed description of the invention.

[0045] Because raising PaCO2 causes global vasodilation, increasing peripheral vascular resistance is key to directing more of the cardiac output generated by CPR to the vital organs, especially the cerebral circulation. A second benefit of raising PaCO2 is a rightward shift in the O2 dissociation curve, which is not present with SNP.

[0046] Another aspect of the invention is a means to control PaCO2 to a desired level by servo control of a mixer that mixes two gases, one with 5 or 5.6% CO2 and the other without. For example, if PaCO2 or PETCO2 is lower than a specified value, the mixer adjusts to deliver a higher CO2 fraction (FCO2). The mixer-monitor feedback mechanism includes a means to slow the change in FCO2 to avoid an under-damped feedback loop that could cause undesirable oscillations in PaCO2. Since FCO2 is not the only parameter that determines PaCO2, (Equation 1) is used to show all the parameters and their interactions.

[0047] (Formula 1)

[0048]

number

[0049] Where: FCO2 is the rate at which CO2 is delivered needed to maintain the desired level of CO2 in the blood.

[0050] PaCO2 (or PETCO2) is the desired partial pressure of CO2 in arterial blood and f is the respiratory rate.

[0051] VT is tidal volume.

[0052] VD is pulmonary dead space, usually 2.2 x body weight in Kg (or body weight in Lbs).

[0053]

number

[0054] is the rate of metabolic production of CO2 in tissues.

[0055] Figure 1a shows the relationship between FCO2 and several ventilation levels (i.e., f and VT).

[0056]

number

[0057] This diagram illustrates the relationship between

[0058] To further evaluate the sensitivity and safety of a new supply of hyperventilation gas mixture, it is necessary to ensure that sufficient oxygen is being supplied. (Equation 2) calculates the effect of the use of this gas mixture on the arterial blood oxygen pressure PaO2.

[0059] (Formula 2)

[0060]

number

[0061] Where:

[0062]

number

[0063] is the metabolic oxygen consumption by the tissue.

[0064] RQ is the respiratory quotient, the ratio of CO2 production to O2 consumption, and is approximately 0.8 in people consuming a balanced diet. FIO2 is the fraction of O2 in the inspired gas.

[0065]

number

[0066] is the alveolar oxygen fraction.

[0067] Even when the O2-hemoglobin dissociation curve is shifted significantly to the right, i.e., when P50=40mmHg (P50 is the oxygen partial pressure at which hemoglobin is 50% saturated), in order to maintain the hemoglobin saturation in the arterial blood close to 100% (e.g., 98%), it is necessary to enrich the mixed gas with oxygen to keep PaO2 and PAlvO2 at levels higher than atmospheric pressure. (Equation 3) is the calculation of the PaO2 required for 98% saturation using the Hill equation.

[0068] (Formula 3)

[0069]

number

[0070] Then, by moving the elements of (Equation 3), we obtain (Equation 4).

[0071]

number

[0072] With O2Sat = 0.98 and P50 = 40, PO2 = 160.6 mmHg is obtained.

[0073] Returning to Equation 2, the minimum values ​​of FIO2, f, and VT for given values ​​of Vdot CO2 and VD can be evaluated. Thus, an important aspect of the present invention is the gas exchange calculator, which helps determine the FICO2 required to maintain PaCO2 for various values ​​of tissue CO2 production. Intuitively, the lower the CO2 metabolic tissue production, the higher the FICO2 must be to maintain PaCO2 at the desired level. Theoretically, this can be done by decreasing alveolar ventilation (e.g., decreasing respiratory rate or tidal volume). However, this leads to limiting oxygen delivery, which may result in PaO2 and O2Sat becoming too low, as shown in Equation 3 and Equation 4. Thus, the gas exchange calculator sets a limit for the minimum alveolar ventilation that is safe for the patient's tissue oxygenation, whatever the level of metabolic rate.

[0074] An additional aspect of the present invention is the delivery of the servo-controlled gas mixture disclosed above not only for breathing, but also to artificial lung and cardiopulmonary bypass machines such as ECMO machines and bubble oxygenators.

[0075] A further aspect of the invention is to maintain artificial ventilation of the patient's lungs at very low, or negative, pressures. This means keeping the mean airway pressure low and minimizing the rise in pressure during inspiration. Doing so reduces the obstruction of lung and thoracic expansion to the venous return of blood from the periphery to the heart and the resistance to blood flow through the pulmonary capillaries. The invention discloses a means of doing so by using a method of endotracheal catheter ventilation to synchronize the inspiratory (lung expansion) phase of the respiratory cycle to the decompression or rebound phase of CPR chest compressions and assisting expiration by applying graduated negative pressure.

[0076] This novel CPR-specific method of optimized ventilation is an integral part of the present invention by focusing on preventing ventilation interference with pulmonary blood flow. A preferred embodiment of the ventilation component consists of the following steps, which when applied together promote venous return to the right heart and filling of the left heart during the "diastolic" or decompression phase of chest compression CPR:

[0077] Synchronize the air injection (inspiration) phase of artificial ventilation with the decompression portion of cardiac massage, thereby facilitating air introduction at a lower driving pressure. The preferred embodiment of this synchronization is to use a high frequency response intratracheal pressure sensor that feeds a processor that determines the correct timing of inspiratory air injection into the lungs at the beginning of the decompression phase of CPR.

[0078] It significantly reduces the anatomical dead space, allowing alveolar ventilation to be maintained with a smaller tidal volume. This is achieved by using a thin tracheal catheter with air aspirated through the main carina. While air is being injected, a balloon near the tip of the catheter is briefly inflated to occlude the trachea and prevent the injected air from escaping. Once the desired volume has been injected, the balloon is deflated, allowing gas to be expelled from the lungs around the catheter (between the catheter and the tracheal wall). This reduces the anatomical dead space by the volume of the upper airway and trachea (~100 ml in adults), and the aerodynamic mixing of the injection jet further reduces the dead space dynamically. This reduces the tidal volume by the amount of dead space reduction, thereby reducing pulmonary pressure and chest expansion.

[0079] It discloses the active expulsion of air from the lungs by applying controlled, graded and synchronized negative pressure to the air outlet (glottis, mouth or nose) using a laryngeal or oronasal mask.

[0080] (definition) The term readily connectable, as used herein, should be construed to include any structure and / or member configured to be conveniently connected to other structures and / or members and / or components of a larger system or assembly. However, the term readily connectable does not necessarily mean easily disconnectable or removable. The term readily connectable is optionally satisfied by providing ease of one-time connection or coupling.

[0081] As used herein, operably connected, operably coupled, or similar terms mean connected in a particular manner (e.g., a manner that allows fluids to move and / or power or signals to be transmitted) that enables the disclosed systems and their various components to operate effectively in the manner described herein.

[0082] As used herein, the terms elastic or resilient are to be construed as relating to essentially ductile materials having a tensile strength less than the aforementioned tensile strengths of flexible or resilient materials, which can be stretched or expanded efficiently at will, and in particular having a UTS value less than about 600 MPa.

[0083] The terms method and process as used herein are to be construed to include any sequence of steps or constituent operations, regardless of a particular chronological order for their execution. The particular steps or constituent operations of any given method or process are not necessarily in the order presented in the claims, description or flow charts of the drawings, unless the context clearly dictates otherwise. Any particular step or constituent operation included in a given method or process may precede or follow any other particular step or constituent operation in that method or process, unless the context clearly dictates otherwise. Any particular step or constituent operation and / or combinations thereof included in any method or process may be performed iteratively before or after any other particular step or operation in that method or process, unless the context clearly dictates otherwise. Furthermore, some steps or constituent operations and / or combinations thereof may be combined, performed together, performed simultaneously, and / or performed in parallel, unless the context clearly dictates otherwise. Furthermore, some steps or constituent operations and / or combinations thereof in any method or process may be skipped, omitted, waived, and / or opted out, unless the context clearly dictates otherwise.

[0084] In this specification or claims, terms implying verb-like actions or operations, whether in the base form, tense, genitive, present / past participle, are to be construed as not necessarily actually being performed, but rather in a constitutive manner, i.e., merely optionally or potentially, performed.

[0085] The term substantially as used herein is a broad term and is to be given its ordinary and accustomed meaning to those of ordinary skill in the art (and is not limited to any special or customized meaning), and refers, without limitation, to a majority, but not necessarily all, of a specified amount or quality.

[0086] The term essentially means that a composition, method or structure may include additional components, steps and / or moieties, but only if the additional components, steps and / or moieties do not materially alter the basic and novel characteristics of the claimed composition, method or structure.

[0087] As used herein, this term has a particular meaning that refers to an interval of plus or minus ten percent (±10%). For any embodiment disclosed herein, disclosure of a particular value in some alternative embodiments is understood to disclose an interval that is about or approximately equal to that particular value (i.e., ±10%).

[0088] As used herein, the terms about or approximately modify a particular value by referring to a range equal to the particular value plus or minus 20% (+ / - 20%). For any of the embodiments disclosed herein, the disclosure of a particular value can also be understood as a disclosure of a range equal to that particular value (i.e., ±20%) in various alternative embodiments.

[0089] However, the terms and operators used herein are also alternative operators equivalent to the term and / or, unless the context clearly indicates otherwise.

[0090] It should be understood, however, that neither the brief summary nor the specific definitions herein are intended to limit interpretation of the invention to any particular form or embodiment, but on the contrary, are intended to cover all modifications, equivalents, and alternatives falling within the scope of the invention.

[0091] Description of the drawings The present invention will be more fully understood and appreciated from the following detailed description taken in conjunction with the accompanying drawings, in which:

[0092] FIG. 1 is a flow diagram of the major physiological events during cardiac arrest and initiation of CPR.

[0093] FIG. 2 is a block diagram of the unified invention.

[0094] FIG. 3 is a schematic diagram of an embodiment of the unified invention.

[0095] Figure 4 is a schematic diagram of an ETCO2-based servo-controlled carbon dioxide enrichment gas delivery system for ventilators and cardiopulmonary bypass.

[0096] Figure 5 shows a schematic diagram of CPR-synchronized ventilation and active exhalation.

[0097] FIG. 6A is a flow diagram of the airway pressure servo controlled ventilation triggering system.

[0098] FIG. 6B is a schematic diagram of the airway pressure servo-controlled ventilation triggering process.

[0099] FIG. 7 is a prior art of endotracheal ventilation according to US7513256.

[0100] FIG. 8A is an example of a distal to proximal sequentially inflated blood loss wrap for CPR.

[0101] FIG. 8B is an example of a spring-loaded one-way valve for distal-to-proximal sequential blood vessel wrap for CPR.

[0102] FIG. 8C illustrates the use of a blood loss wrap that is inflated sequentially from distal to proximal for CPR.

[0103] FIG. 9A is an example of a distal-to-proximal rolling blood removal rotation device for CPR.

[0104] FIG. 9B is an example of an assembly for a distal-proximal split sleeve sequential wrap tourniquet for CPR.

[0105] FIG. 9C is an example of a near-complete assembly and completed distal-to-proximal split sleeve sequential wrap CPR tourniquet.

[0106] FIG. 10A shows the fraction of carbon dioxide in the delivered gas required to achieve four exemplary levels of arterial PCO2-PaCO2--FCO2 as a function of tissue carbon dioxide production rate--VdotCO2.

[0107] FIG. 10B shows the fraction of carbon dioxide in the insufflated gas required to achieve an arterial PCO2-PaCO2 of 55 mmHg, FCO2, as a function of the tissue carbon dioxide production rate, VdotCO2, for four exemplary tidal volumes, VT.

[0108] FIG. 10C shows the fraction of carbon dioxide in the insufflated gas required to achieve an arterial PCO2-PaCO2 of 55 mmHg, FCO2, as a function of the tissue carbon dioxide production rate, VdotCO2, for the four exemplary respiratory rates, f.

[0109] FIG. 10B shows the fraction of carbon dioxide (FCO2) required in the delivered gas to achieve an arterial blood PCO2 (PaCO2) of 55 mmHg with an exemplary four-stage dead space (VD) as a function of tissue carbon dioxide production rate (VdotCO2).

[0110] FIG. 11A shows the fraction of oxygen in the insufflation gas, FO2, required to achieve four exemplary levels of arterial blood oxygen pressure, PaO2, as a function of the tissue molecular oxygen consumption rate, VdotO2.

[0111] FIG. 11B shows the molecular oxygen fraction FO2 in the insufflated gas required to achieve an arterial blood oxygen pressure PaO2 of 161 mmHg as a function of the tissue molecular oxygen consumption rate VdotO2 at four exemplary tidal volumes VT.

[0112] FIG. 11C is the molecular oxygen fraction FO2 in the insufflated gas required to achieve an arterial blood oxygen pressure PaO2 of 161 mmHg with four exemplary levels of respiratory rate f as a function of tissue molecular oxygen consumption rate VdotO2.

[0113] FIG. 11D is the molecular oxygen fraction FO2 in the delivered gas required to achieve an arterial blood oxygen pressure PaO2 of 161 mmHg with four exemplary levels of dead space VD as a function of tissue molecular oxygen consumption rate VdotO2.

[0114] FIG. 12A is an exemplary operating procedure for the gas exchange calculator.

[0115] FIG. 12B illustrates the relationships between the parameters.

[0116] While the invention is susceptible to various modifications and alternative forms, specific embodiments thereof are shown by way of example only in the drawings, which are not necessarily complete and the components are not necessarily to scale, emphasis instead being placed upon clearly illustrating the underlying principles of the invention.

[0117] (Detailed disclosure of embodiments) According to the present invention, three measures are used to optimally treat a cardiac arrest patient undergoing cardiopulmonary resuscitation (CPR) to maximize the amount of oxygen reaching the brain. FIG. 2 is a schematic block diagram of the present invention, which is integrally and inseparably composed of three elements. As will be explained herein, these elements interact clinically and physiologically to enhance the overall effect on oxygen delivery to the brain, but also, in the absence of one of the elements, the effect of the other elements may be detrimental, causing more harm than good. This is best understood by considering the shortcomings of the current technology of performing CPR as outlined in the block diagram of FIG. 1, following the teachings of the American Heart Association.

[0118] The left side of Figure 1 outlines the physiological events immediately following the onset of cardiac arrest. The right side shows the outcome of current treatments collectively referred to as cardiopulmonary resuscitation (CPR). As a result, as mentioned in the introduction, in many cardiac arrest patients treated with current treatments, the heart resumes beating (also known as return of spontaneous circulation (ROSC)), but the brain suffers catastrophic and irreversible damage. The overall result is that only a minority of patients who undergo CPR experience meaningful survival with acceptable mental function. The sequence of events begins with the acute event of cardiac arrest11 and the associated cessation of cardiac output12. As a result, two major events occur: oxygen is no longer delivered to all tissues14, and the sympathetic nervous system, the function that controls smooth muscle tone in arterioles and other blood vessels, ceases13. The lack of blood flow to all tissues15 causes compensatory vasodilation18, also known as reactive hyperemia17, which adds to the effects of sympathetic arrest13 and the resulting loss of vasomotor tone16. Extreme vasodilation 18 reduces total peripheral resistance 19, causing a fall in blood pressure and flow when cardiac massage is initiated as part of CPR. Peripheral vasodilation causes pooling of blood in the periphery, with most of the blood not returning to the heart and filling the ventricles 37. Summarizing the left side of the diagram, it can be simply said that cardiac arrest causes extreme vasodilation.

[0119] When CPR22 is administered, the patient receives chest compressions23 at a rate of 100 per minute, artificial positive pressure ventilation24, and injection of epinephrine36 according to current AHA protocols. When effective chest compressions are initiated, some cardiac output27 and oxygen delivery28 are generated. This reverses to some extent the mechanisms that cause reactive hyperemia29 and subsequent vasoconstriction34. Intravenous injection of epinephrine36 also causes vasoconstriction34, but this is primarily constriction of cerebral blood vessels31. Initiation of positive pressure ventilation IPPV24, even at 1-2 breaths per 15 compressions, i.e. 6-12 breaths per minute, removes more CO2 from the lungs than is produced in the tissues25, rapidly reducing the arterial partial pressure of CO2, known as hypocapnia30. Hypocapnia30 directly affects cerebral circulation by causing vasoconstriction31 and greatly reducing cerebral blood flow32 and oxygen transport35. Hypocapnia also causes a shift in the oxygen-hemoglobin dissociation curve to the left, meaning that for every milliliter of blood flowing through the tissues, less oxygen escapes the hemoglobin and is delivered to the tissues, contributing to reduced oxygen delivery to the brain, among other tissues.

[0120] Another deleterious effect of positive pressure ventilation (IPPV) is the expansion of the lungs and chest and the increase in intrathoracic pressure. The increase in intrathoracic pressure during IPPV further reduces venous return to the right side of the heart by decreasing the pressure gradient from the extrathoracic veins to the intrathoracic vena cava segments. At the same time, the expansion of the lungs by IPPV leads to an increase in pulmonary vascular resistance, impeding blood flow from the right to the left side of the heart, thereby reducing venous return to the left ventricle. The well-known reduction in biventricular filling caused by IPPV, combined with the reduction in venous return due to peripheral pooling, reduces the cardiac output achieved by chest compressions during CPR by 1 / 300 of the normal amount. rd The end result is a further reduction in blood flow and oxygen transport to the brain.

[0121] Based on the above information, it is clear that the combined use of positive pressure ventilation and epinephrine in the presence of very low cardiac output critically reduces oxygen delivery to brain tissue. Thus, the present invention teaches that to protect the brain from injury, CPR must use the exact opposite approach: it must induce and maintain vasodilation focused on the cerebral circulation, it must compress and constrict peripheral vessels, it must absolutely avoid the blood flow obstruction to the heart caused by IPPV, while shifting the O2-hemoglobin dissociation curve to the right instead of the left. The patent teaches how to do this by combining the following processes:

[0122] A schematic block diagram of the unified invention is shown in Figure 2. The most powerful and natural means of dilating arterioles and other blood vessels is to induce hyperventilation, which is an increase in carbon dioxide CO2 partial pressure. This can be easily done by supplying carbon dioxide enriched gas 101 to the ventilator circuit and, if used, to the gas exchanger of a heart-lung machine such as an ECMO or bubble oxygenator. As briefly mentioned in 101, enriched CO2 induces vasodilation and shifts the O2-hemoglobin dissociation curve to the right to promote O2 transfer to cells and their mitochondria, stimulating the patient's respiratory drive. However, CO2-induced vasodilation is totally useless by itself, since it is global and leads to blood pooling in the periphery. It is necessary to include a means 107 to counteract peripheral vasodilation. The present invention teaches the combination of the use of a means of squeezing blood from the periphery to the core by applying sequential distal-proximal autotransfusion, and a means of preventing blood return to the periphery by acting as a tourniquet 103. The combined effect of the tourniquet 103 is to increase the preload on the heart by shifting blood from the periphery to the core, while restricting flow to the periphery, redirecting the flow created by CPR to essential organs and minimizing shunting of blood that creates a higher resistance to flow, also known as the cardiac afterload.

[0123] Increasing venous return to the right heart by sequentially squeezing the limbs as taught in 103 does not completely overcome the blood flow impairment caused by IPPV 111. This means that the ventilation 105 must be modified to minimize the increase in pressure and inflation during ventilation. To this end, the present invention teaches minimizing tidal volume by injecting inspiratory fresh gas into the distal trachea and reducing anatomical dead space by synchronizing with CPR decompression (passive or active). The inventive components of 105 also disclose the application of negative pressure (suction) during the expiratory phase of the ventilation cycle. They also teach reducing the tidal volume-VT to a level sufficient to achieve arterial oxygen saturation of 98% or higher. This is done according to the mathematical algorithm described in Figures 11a, 11b, 11c and 11d, which takes into account all factors that affect O2 transport, such as tidal volume, dead space, respiratory rate, arterial PCO2, P50 (position of the O2 dissociation curve), rate of O2 consumption by tissues, use (if any) and effectiveness of a cardiopulmonary bypass machine.

[0124] The ventilation scheme described in 105 closely interacts 109 with the CO2 supply described in 101 through servo-control of the CO2 fraction FCO2 supplied in the inhaled gas or in the heart-lung exchanger. Whatever the CO2 partial pressure in 101, FCO2 is influenced by the ventilation parameters in 105 and vice versa.

[0125] The combined effect of all three poles of the present invention effectively affects the cerebral blood flow extent of O2 transport to brain tissue 120, as shown diagrammatically by the process indicated by interlocking arrows 113, 115, 117.

[0126] To better understand the interrelated poles of the invention, reference is now made to FIG. 3, in which a CPR chest compression 130 of a cardiac arrest victim is shown. First, a distal-to-proximal limb compression and hemostasis device 132 is pointed out, which is applied sequentially. This is the means by which the vasodilatory effect of the CO2-enriched gas is counteracted and blood is prevented from moving from the limbs to the trunk and back. It is understood that such a limb compression device can also be applied to the victim's arm without being shown in the drawing. Next, a gas mixer 142 is shown which is servo-controlled by receiving continuous information on the end-tidal CO2 level during expiration via wired or wireless communication 160. This end-tidal CO2 is tracked by a CO2 analyzer 152 in direct communication 150 with a face or laryngeal mask 164 through which the expired gas is transmitted. The CO2 partial pressure level at the end of expiration corresponds to the arterial partial pressure of CO2 and can therefore be used to servo-control the gas mixture by the mixer 142 which is delivered to the ventilator 144 via conduit 146. Another embodiment of this portion of the invention is to use a transcutaneous CO2 monitor or an indwelling arterial CO2 electrode, not shown in this drawing. Yet another embodiment of the invention is by splitting the gas mixture passing through conduit 146 and feeding a portion of it to the gas exchanger of a heart-lung machine 163, also not shown in FIG. 3. A servo-controlled gas mixer 142 mixes gas from multiple compressed gas cylinders 134 and 136 connected to the mixer 142 via corresponding conduits 138 and 140. In a preferred embodiment, one cylinder contains compressed pure (100%) oxygen and the other cylinder contains a 5% CO2 mixture, also known as carbogen. By mixing the two gases in any proportion, FCO2 levels between 0.0 (if all gas is supplied from 100% oxygen) and 0.05 (if all gas is supplied from the mixing cylinder) can be produced. Other embodiments consist of higher CO2 concentrations in the mixing cylinder, including levels of 5-6% or 6-8%. Additionally, in some embodiments, an inert gas such as xenon or argon is added to the O2 gas mixture at a ratio of 35% to 45% O2, resulting in an inert gas level of 65% to 55%.To ensure that the patient always receives sufficient oxygen, the inert gas-carbogen mixture should contain an equal percentage of oxygen.

[0127] Next, the elements used to ventilate the patient in a manner that does not impede blood flow to the chest and through the lungs are disclosed in FIG. 3. These are regulated and servo-controlled by a high fidelity pressure sensor 148 in communication 166 with the patient's airway. This signal is analyzed by a computer-based algorithm, shown in FIG. 6a, which decides when to initiate breathing with the synchronized positive pressure ventilator 144 or when to start vacuuming out gas with the pump 162. In a preferred embodiment, the positive pressure ventilator 144 injects gas into the distal trachea via a thin catheter 150 with an inner diameter of 4±1 mm. As soon as gas begins to flow into the catheter 150, an elastic balloon 151 inflates to occlude the trachea and prevent air from escaping. This endotracheal ventilation is described in detail in FIG. 7 and in U.S. Pat. No. 7,513,256. Injecting gas at the distal trachea and allowing it to escape around the catheter 150 ensures that the fresh gas interface moves deeper from the airway opening (mouth / nose), thereby cutting the dead space by approximately 100 cc in an adult. This cuts the tidal volume by the same amount, reducing lung and chest expansion. Another element of this preferred embodiment is the active evacuation of gas through the mask 164 and conduit 150 assisted by a regulated and synchronized vacuum pump 162, which is servo-controlled 156 by a signal from the airway pressure sensor 148.

[0128] It is now possible to further illustrate the end-tidal CO2-based servo control of the gas composition delivered to the ventilator and heart-lung machine, as shown in Figure 4. In this figure, the focus on gas delivery reduces clutter. The ventilator 158 and the heart-lung machine exchanger 163 receive gas from a servo-controlled gas mixer 142, which mixes multiple gases 134 and 136 delivered from compressed gas cylinders via conduits 138 and 140. The mixed gas receives a signal from an end-tidal CO2 monitor 152 and adjusts the level of CO2 in the mixed gas to ensure that the partial pressure ETCO2 is at the desired level. It is clear to experts in the field that if the CO2 level in the expired gas is higher than the desired level, the FCO2 in the gas must be decreased, and if it is lower than the desired level, the FCO2 in the mixed gas must be increased. The feedback control is done so that the changes are made effectively fast enough, but not too fast, to avoid undesired fluctuations in CO2 (under-damped feedback loop).

[0129] Another part of the description of the invention is shown in FIG. 5, where the inlet and outlet of air to the lungs are synchronized with the airway fluctuations caused by CPR chest compressions. The preferred embodiment is based on the use of a compression signal obtained by an intra-airway pressure sensor 148, which is inserted into the airway or connected to the airway lumen via a conduit 166. The pressure sensor must be sensitive to the airway pressure changes induced by CPR chest compressions, with a sufficient frequency response of 0 Hz to 100 Hz, or 0 Hz to 1000 Hz. The pressure sensor may be standalone or may be integrated into the air delivery catheter 150. Another preferred embodiment uses a signal from a chest motion accelerometer that tracks the vertical movement of the chest wall. Yet another embodiment uses a signal from a chest motion accelerometer that tracks the vertical movement of the chest wall in the lower third of the esophagus. rdThe pressure signal is obtained from an esophageal pressure sensor located in the esophageal cavity. In another preferred embodiment, central venous pressure (CVP) is used to monitor and track changes in intrathoracic pressure due to CPR chest compressions. It will be apparent that any combination of such sensors can be used to obtain more accurate and reliable data for triggering the start of inspiration delivered by the positive pressure ventilator 144 and active expiratory vacuum pump 162. The trigger signal is used in the preferred embodiment to initiate the delivery of gas according to a flow diagram algorithm shown diagrammatically in Fig. 6a and Fig. 6b. The pressure signal is also used to initiate and control the evacuation of air from the lungs by ensuring that the airway pressure is kept gentle sub-atmospheric but not too low, in the range of -2 to -7 cmH2O. Control of the vacuum is performed by opening and closing a solenoid valve or MEMS component, or by controlling the speed of an electric or electromagnetic vacuum pump. The control and operation of the evacuation pump is not shown in the drawings. A preferred embodiment of a gas delivery positive pressure ventilator 144 is shown in Figure 7 as an endotracheal ventilation device previously patented in US Patent No. 7,513,256. Other types of externally triggerable volume or pressure ventilators may also be used.

[0130] A preferred embodiment of the algorithm used to convert a pressure signal into an airflow activation trigger is shown in FIG. 6a. A signal corresponding to an instantaneous chest compression is obtained as an airway pressure signal at 170. As disclosed above, other signals such as chest wall acceleration, proximity signals, light reflex signals, auxiliary signals from mechanical compression devices, tracheal tube signals or intravascular pressure signals can also be used. A time-averaged value of chest pressure or position is calculated over time at 172 to determine a reference point. This can be done digitally or with an analog integrator. As long as the chest diameter or pressure signal indicates that it exceeds said average value Pmaw, determined using the "if" box 174, the algorithm path loops through 184 to continue acquiring signals through 170. This loop is repeated until the value of the chest diameter or pressure indicates that the chest diameter is below Pmaw. When this is detected, a secondary test is applied by 176 to ensure that the chest diameter or pressure is trending in the direction of further decrease by calculating the first derivative of the chest diameter or pressure signal. If the gradient does not point towards a continued decrease in diameter or pressure, the loop continues to 170 via path 184. Once both the actual size and the size derivative indicate the beginning of the chest decompression phase, the algorithm then checks whether it is the right time to initiate a breath 178. If not, the loop continues from path 184 through 170 at a sufficient rate, e.g., every 5 msec. Once the check of 178 detects that it is time to initiate a breath, the algorithm initiates an inspiration 182 by determining the time elapsed since the previous breath (e.g., 5 seconds, 10 seconds, 12 seconds) or the number of chest compressions since the previous breath (e.g., 15, 7, 8). This is done by actuating a direct airflow into the patient's trachea via an inserted catheter or tube, an example of which is shown in FIG. 7. Thereafter, a timer or volume counter or pressure signal from the airway is activated and when a threshold is set indicating that sufficient gas has been insufflated into the lungs, an end of breath decision 180 is activated, air injection is stopped and control path 186 returns the algorithm to repeat the process at 170.

[0131] A schematic example of the breath initiation process is shown in FIG. 6B, which for clarity is organized into three panels. Panel A 202 shows the anteroposterior (AP) diameter of the chest 196 as a continuous trace 198. When the trace is pointing upwards ("OUT") 192, it means that the chest diameter is increasing. In this Panel A, the decompression is due to passive elastic recoil of the chest wall. The time axis 194 shows the elapsed time in seconds from an arbitrary time zero. The second trace in Panel A (labeled 200) shows the airway pressure (Paw) 190 in cmH2O, with zero referenced to atmospheric pressure. It can be seen that as the chest is compressed (in) the pressure increases, and as the chest is decompressed (out) Paw decreases, and may even become negative relative to atmospheric pressure.

[0132] Panel B similarly shows the movement of the chest in the upper traces, both as a passive recoil 210 as in panel A, and as an active suction or vacuum mechanism is activated 208, pulling the chest outwards. Both traces 208 and 210 refer to the chest diameter axis on the left side of the panel. The active decompression can actually expand the chest to have a higher AP diameter and volume than would be the case with passive recoil. Furthermore, as shown in pressure trace 211, this can bring the airway pressure below atmospheric levels, as referenced to the second Y-axis on the right side. Timing gas delivery to the lungs to coincide with this negative decompression phase clearly shows the advantage of the present invention over the prior art, which does not synchronize chest compressions with gas delivery, resulting in higher intrathoracic and airway pressures. As explained earlier, this has the advantage of minimizing the obstruction to blood flow from the main veins to the right side of the heart. This is shown diagrammatically in Panel C, where the algorithm detects that (a) the pressure is negative and (b) the pressure is monotonically decreasing (positive dp / dt), thus triggering the start of a breath 212. The balance between the negative pressure in the deflated chest 216 and the positive pressure of the delivered gas gives a smaller pressure trace 214 than if synchronization had not been achieved.

[0133] FIG. 7 incorporates the teachings of US Pat. No. 7,513,256 as an optimal and preferred embodiment for combination with the other two modalities of this patent. Other positive pressure ventilation modes can be used, and triggered breath initiation is possible, but may not have sufficient response time to accurately synchronize with 100 breaths per minute CPR. The endotracheal ventilator operates with a thin catheter that is half the size of a normal endotracheal tube. To reduce the diameter by half, the amount of air in the ventilator, which requires 16 times the driving pressure, is also 16 times smaller (according to Boyle's law). This means that the size of the ventilator can be reduced by the same proportion, resulting in a very fast frequency response, making it very suitable for cardiopulmonary resuscitation and synchronized ventilation. Furthermore, because the air outflow is around a thin tube, a much larger cross-sectional area is available for lung exhaust, dramatically reducing the lung exhaust resistance during the expiratory phase of the ventilation cycle. This further reduces the average lung and thoracic volume, reducing the impairment of blood return to the right heart. The incorporation of a vacuum pump to add synchronized active gas evacuation further reduces lung and thoracic volume. It should be noted that any method of venous aspirating by negative intrathoracic pressure, whether through active chest decompression, the use of an inspiratory threshold device, or application of vacuum during expiration, is substantially flow-limited by the collapsible nature of large veins. It is therefore necessary to apply the third component of this invention, namely, sequential distal-to-proximal limb compression as shown in Figures 8 and 9.

[0134] The practice of shifting blood from the extremities to the trunk in emergency situations has been around for a long time. Leg elevation has been described in ancient literature and is in fact used in orthopedic surgery as a means of exsanguination before the application of a pneumatic tourniquet to create a bloodless surgical field. A study by Blond et al. published in Acta Orthopedica Scandinavia in 2001-2 showed that limb elevation shifts approximately 45% of the blood out of the extremities; this means that 55% of the blood remains in the extremities. Attempts to use medical anti-shock pants for this purpose were unsuccessful (Bickel et al. 1987 Jun;16(6):653-8.), a device called Hemaclear (RTM) www.hemaclear.com is widely used in orthopedic surgery to shift blood from the extremities to the trunk and prevent it from re-entering, and a similar device called Hemashock (RTM) www.hemashock.com is available for emergency use. The present invention discloses two additional devices that are uniquely suited to counteract the vasodilatory effects of carbogen use as part of this CPR mode during cardiac arrest by rapidly and effectively squeezing blood from distal to proximal, priming the heart while increasing afterload, diastolic blood pressure, coronary perfusion pressure, and most importantly, cerebral blood flow.

[0135] FIG. 8A discloses a pneumatic distal-proximal sequentially inflatable CPR blood loss wrap 250 for application to a single limb. The device is comprised of multiple inflatable bladders 264 embedded in a fabric bandage 262. The bladders are rectangular or parallelogram shaped 266 to facilitate optimal coverage and compression of the limb when inflated. The wrap is quickly applied to the limb and closed with a hook-and-loop fastener 256 or similar secure and adjustable closure. Inflation begins with the most distal compartment, preferably by connecting a compressed gas bottle controlled by a flow regulator 258 and a pressure regulator 260. When the pressure in the most distal bladder reaches a preset level controlled by a spring-loaded one-way valve 274 as shown in FIG. 8b, the second bladder begins to fill until all compartments are inflated to the desired pressure. In this way, the wrap sequentially compresses the limb from distal to proximal. In another embodiment, it can be inflated using a manual or electric pump (not shown). The wrap deflation process should be step-wise from proximal to distal. The bladders should be deflated one at a time and the patient's vital signs should be assessed after each bladder is deflated. The bladders are deflated by applying a vacuum from the vacuum pump 254 through thick walled tubing 270 connected to regulator 272 and valve 268. Note that after the most proximal bladder is emptied, the spring loaded one-way valves between the bladders will only open when the vacuum level is higher than the threshold that opens the spring loaded valves. Therefore, the bladders are deflated one at a time as needed.

[0136] A preferred embodiment of a pressure regulated one-way valve between the bladders is shown in the schematic diagram 280 of FIG. 8b. The valve plate 290 is tensioned by a spring 286 that is firmly attached at its underside to a palisade-like rigid support 282. When closed, the plate 286 rests snugly against a circular ledge 288, and a resilient cushion O-ring 284 acts as a seal between the spring-loaded plate 290 and the closure ledge 288. As shown in FIG. 8a, there is a spring-loaded one-way valve between every bladder. To open, the pressure difference between the lower and upper ends (distal and proximal ends) of the valve must be sufficient to overcome the pulling force of the spring, which in the preferred embodiment is greater than 200 mmHg. In other embodiments, the spring force is set to require a pressure difference of 100-150 mmHg, 150-200 mmHg, 200-300 mmHg. The pressure difference can be created by inflating the distal bladder above the valve opening threshold or by applying a vacuum above the valve opening threshold. As shown in FIG. 8c, we further disclose the ability to apply wraps 292 to each leg. This is done by connecting each wrap or wraps with inflation tubes as shown at 294 and 296 which connect to a compressed gas cylinder 298 via a pressure regulator 300. It is clear that smaller size wraps of a similar design can be applied to the arms if necessary. A healthy person's blood volume in both arms is 150 ml and that in both legs is over 500 ml, but the volume can be much higher if blood pools in the peripheral vessels during cardiac arrest.

[0137] A new configuration of an elastic tourniquet as shown in FIG. 9 is now described. The device is similar to the previously patented HemaShock in its general configuration consisting of an elastic ring wrapped with an elastic sleeve, which rolls up the limb when a strap, which also wraps around the ring, is pulled. The unique configuration of the new device is that it does not include a strap. The device 302 is rolled from distal to proximal by pulling on the strap 310 or split sleeve 308 shown in FIG. 9b. The preferred embodiment of this CPR tourniquet device consists of an initially complete sleeve 306 wrapped around an elastic ring made of elastic stretchable silicone or metal (steel) spring 304. The steel spring ring and rolled sleeve 316 are rolled up around the limb by pulling on the strap 310. When the patient is ready to remove the tourniquet, it is manually rolled in stages from proximal to distal while monitoring the patient's vital signs to avoid cardiovascular collapse.

[0138] We now turn to an important safety feature of the gas exchange calculator, governed by (Eq. 5) and (Eq. 6) and using the parameter input calculator of FIG. 12a as shown in the output of FIG. 12b. Although the continuous adjustment of the servo-controlled gas mixer 142 is based on feedback from the end-tidal CO2 monitor 152, it is safer and more practical to adjust its initial settings and boundaries based on physiological parameters. The gas exchange calculator shown in FIG. 12a determines these initial settings by inputting the patient's own parameters. Starting at 350 in FIG. 12a, the user first inputs the patient's weight 352, followed by the ventilation rate 354 and the volume of each breath, known as the tidal volume 356. The user then inputs information about the ventilation method, from which the calculator determines the size of the dead space VD 358. For example, the dead space VD for a healthy person breathing spontaneously is approximately 2.2 ml / kg. However, when ventilating with a mask, the air in the mask is rebreathed, which adds to the normal anatomical VD, resulting in approximately 3.2 ml / kg. When the patient is intubated with an endotracheal tube, the upper airway is bypassed and the VD is reduced to 1.5 ml / kg. Finally, if endotracheal ventilation is used, the VD is reduced to 0.7 ml / kg. The user then inputs the target PaCO2 360. The effects of ambient air pressure and water vapor partial pressure are input in 362 and 364, and the actual water vapor partial pressure is determined according to the patient's temperature. The fraction of inspired oxygen, FIO2, is then set by the user 366. The unknown parameter during CPR is the amount of CO2 the patient is actually producing by metabolism 368. In a healthy resting state, this is 2.8 ml / kg / min. An estimate of the actual value during CPR is determined based on the cardiac output generated by the CPR chest compressions. If the cardiac output is 0.3 of the normal cardiac output, the estimate of the metabolic level should be around 0.3.

[0139] Using these parameters, the gas exchange calculator determines the required level of FICO2 via (Equation 5) and the expected PaO2 via (Equation 6). (Equation 5) calculates the required FICO2 required to maintain PaCO2 at the desired level, as shown in FIG. 12b, line 386. From the graph, it can be seen that the lower the metabolic production of CO2, as shown on the horizontal axis 388, the higher the FICO2, as shown on the left vertical axis 382, ​​should be. If metabolism were to completely stop and CO2 production were to go to zero, the FICO2 should be higher than 0.05. As an example, if the metabolic rate is about 1 / 3 of normal, as shown by the vertical dashed line 374, the FICO2 required to maintain PaCO2 at a level of 55 mmHg, which we will use as a target in this example, should be about 0.04 (4%), as shown by the horizontal dashed line 378.

[0140] We now turn our attention to the required concentration of oxygen in the inspired gas. Equation 6 calculates the predicted PaO2 from the parameters entered into the gas exchange calculator. Equation 3 gives the minimum PaO2 required to achieve oxygen saturation of at least 98%. This value is higher than normal because the Bohr effect of a higher PaCO2 concentration, with a P50 of 40 mmHg instead of the normal 26.6 mmHg, shifts the O2-hemoglobin dissociation to the right. Using Equation 3, we see that a lower limit of PaO2 of 161 mmHg is required. Looking next at Equation 6 and the graph in Figure 12b, we see that line 380 predicts the PaO2. We also see that at the working point indicated by the vertical dashed line 374, the value of line 380 where it intersects with the horizontal dashed line 376 is approximately 240 mmHg. This value is higher than the previously mentioned lower safe limit of 161 mmHg. These parameters can be used in the gas exchange calculator. However, if a combination of parameters is selected such that the PaO2 at the working point is lower than 161, the calculator will generate an alarm signal. Thus, the gas exchange calculator is an essential safety feature when using gas mixtures with high FICO2 values.

[0141] (Formula 5)

[0142]

number

[0143] (Formula 6)

[0144]

number

[0145] [Table 1] [Brief description of the drawings]

[0146] [Figure 1] FIG. 1 is a flow diagram of the main physiological events during cardiac arrest and initiation of CPR. [Diagram 2] FIG. 1 is a block diagram of a unified invention. [Diagram 3] FIG. 1 is a schematic diagram of an embodiment of the unified invention. [Figure 4] FIG. 1 is a schematic diagram of an ETCO2-based servo-controlled carbon dioxide enrichment gas supply system for ventilators and cardiopulmonary bypass. [Diagram 5] Schematic diagram of CPR-synchronized ventilation and active exhalation. [Figure 6A] FIG. 1 is a flow diagram of an airway pressure servo controlled ventilation triggering device. [Figure 6B] FIG. 1 is a schematic diagram of the airway pressure servo-controlled ventilation triggering process. [Figure 7] Prior art of endotracheal ventilation according to US7513256. [Figure 8A] FIG. 1 is an example of a distal-to-proximal sequentially inflated blood loss wrap for CPR. [Figure 8B] FIG. 1 is an example of a spring-loaded one-way valve for distal-to-proximal sequential blood vessel wrap for CPR. [Figure 8C] An example of the use of a distal to proximal sequentially inflated blood loss wrap for CPR. [Figure 9A] FIG. 1 is an example of a distal-to-proximal rolling blood loss rotating device for CPR. [Figure 9B] This is an example of the assembly of a distal-proximal split sleeve sequential wrap tourniquet for CPR. [Figure 9C] 1 is an example of a near-complete assembly and a completed distal-to-proximal split sleeve sequential wrap CPR tourniquet. [Figure 10A] 1 shows the fraction of carbon dioxide in the delivered gas required to achieve four exemplary levels of arterial PCO2-PaCO2-FCO2 as a function of tissue carbon dioxide production rate-VdotCO2. [Figure 10B] 1 shows the fraction of carbon dioxide in the insufflated gas required to achieve an arterial PCO2-PaCO2 of 55 mmHg, FCO2, as a function of the tissue carbon dioxide production rate, VdotCO2, for four exemplary tidal volumes, VT. [Figure 10C] 1 shows the fraction of carbon dioxide in the insufflated gas required to achieve an arterial PCO2-PaCO2 of 55 mmHg for four exemplary respiratory rates f, as a function of the tissue carbon dioxide production rate VdotCO2. [Figure 10D] FIG. 1 shows the fraction of carbon dioxide (FCO2) required in the delivered gas to achieve an arterial blood PCO2 (PaCO2) of 55 mmHg with four exemplary stages of dead space (VD) as a function of tissue carbon dioxide production rate (VdotCO2). [Figure 11A] 1 shows the fraction of oxygen in the insufflated gas, FO2, required to achieve four exemplary levels of arterial blood oxygen pressure, PaO2, as a function of tissue molecular oxygen consumption rate, VdotO2. [Figure 11B] The molecular oxygen fraction FO2 in the insufflated gas required to achieve an arterial blood oxygen pressure PaO2 of 161 mmHg is shown as a function of the tissue molecular oxygen consumption rate VdotO2 at four exemplary tidal volumes VT. [Figure 11C] is the molecular oxygen fraction FO2 in the insufflated gas required to achieve an arterial blood oxygen pressure PaO2 of 161 mmHg using four exemplary levels of respiratory rate f as a function of the tissue molecular oxygen consumption rate VdotO2. [Figure 11D]is the molecular oxygen fraction FO2 in the delivered gas required to achieve an arterial blood oxygen pressure PaO2 of 161 mmHg with four exemplary levels of dead space VD as a function of tissue molecular oxygen consumption rate VdotO2. [Figure 12A] 1 is an exemplary operating procedure for a gas exchange calculator. [Figure 12B] This is a diagram showing the relationship between parameters.

Claims

1. 1. A system for safely delivering an efficient amount of oxygen to a needed organ during cardiopulmonary resuscitation (CPR), comprising: (a) at least one limb compression device configured to apply a compressive force sequentially from distal to proximal to a limb to occlude blood flow to the limb; (b) a positive pressure ventilation subsystem configured to deliver the mixed gas under positive pressure; the positive pressure ventilation subsystem comprising: (I) a carbon dioxide reservoir containing carbon dioxide enriched gas; (II) a molecular oxygen reservoir containing a molecular oxygen enriched gas; (III) a controllable mixing module operably connected to the carbon dioxide reservoir and the molecular oxygen reservoir and configured to controllably mix the molecular oxygen enriched gas with the carbon dioxide enriched gas; (IV) at least one carbon dioxide partial pressure sensor selected from the group consisting of an arterial blood carbon dioxide partial pressure sensor and an end-tidal carbon dioxide partial pressure sensor, the carbon dioxide partial pressure sensor configured to detect the carbon dioxide partial pressure in arterial blood; (V) a controller operatively connected to the controllable blending module and the at least one carbon dioxide partial pressure sensor, the controller configured to control at least one ratio selected from the group consisting of a ratio of the molecular oxygen enriched gas and a ratio of the carbon dioxide enriched gas in the mixture of the molecular oxygen enriched gas and the carbon dioxide enriched gas; (VI) an endotracheal tube including a sealing cuff disposed on a distal portion thereof, the endotracheal tube being configured to repeatedly assume; The endotracheal tube comprises: (i) a deployed configuration, in which the sealing cuff engages an inner surface of the trachea, thereby effectively sealing a gas passage between the sealing cuff and the inner surface of the trachea while maintaining the flow of gas from the endotracheal tube into the trachea; (ii) a retention configuration in which the sealing cuff disengages from the interior surface of the trachea while maintaining natural outflow of the gas from the trachea; The system further comprises: (c) a myocardial stimulation device configured to restore spontaneous circulation of the arterial blood by applying at least one type of stimulation selected from the group consisting of mechanical stimulation and electrical stimulation to the myocardium at predetermined time intervals; (d) a tracheal pressure sensor configured to continuously measure pressure within the trachea; and (e) a synchronizer configured to time an inflation phase of the positive pressure ventilation system with the start of a depressurization phase of the cardiac stimulation.

2. 10. The system of claim 1, wherein the distal to proximal sequential compressive force on the limb is accomplished by up-rolling contracting elastic rings.

3. 2. The system of claim 1, wherein the distal to proximal sequential compressive force on the limb is achieved by applying at least one element selected from the group consisting of an elastic bandage, an elastic limb wrap with an adjustable closure, and an inflatable limb wrap with an adjustable closure.

4. 10. The system of claim 1, wherein the at least one limb compression device is configured to occlude arterial inflow of blood to the limb by applying a surface skin pressure range selected from the group consisting of 100-200 mmHg and 200-300 mmHg.

5. The mixed gas is 95% molecular oxygen and 5% carbon dioxide, 0.1-2.0% carbon dioxide, the rest molecular oxygen, 2.1-4.0% carbon dioxide, the remainder molecular oxygen, 4.1-5.6% carbon dioxide, the rest molecular oxygen, 0.1-5.0% carbon dioxide, 30-50% molecular oxygen, and the remainder the chemical element xenon.

2. The system of claim 1, wherein the gas is selected from the group consisting of 0.1-5.0% carbon dioxide, 30-50% molecular oxygen, and the remainder chemical element argon.

6. 2. The system of claim 1, wherein the controllable mixing module controllably mixes a gas mixture of 5% carbon dioxide and 95% molecular oxygen with pure 100% molecular oxygen according to feedback from the at least one carbon dioxide partial pressure sensor selected from the group consisting of the arterial blood carbon dioxide partial pressure sensor and the end tidal carbon dioxide partial pressure sensor, to maintain the arterial blood carbon dioxide partial pressure level at 41-45 mmHg.

7. the controllable mixing module controllably mixes a gas mixture of 5% carbon dioxide and 95% molecular oxygen with pure 100% molecular oxygen according to feedback from the at least one carbon dioxide partial pressure sensor selected from the group consisting of the arterial blood carbon dioxide partial pressure sensor and the end tidal carbon dioxide partial pressure sensor; 2. The system of claim 1, wherein the arterial blood carbon dioxide partial pressure sensor and the end tidal carbon dioxide partial pressure sensor maintain the arterial blood carbon dioxide partial pressure level in at least one pressure range selected from the group consisting of 41-45 mmHg, 46-50 mmHg, 51-55 mmHg, and 56-65 mmHg.

8. 2. The system of claim 1, wherein the controllable mixing module controllably mixes a gas mixture of 5% carbon dioxide, 30% molecular oxygen and 65% elemental xenon with a gas mixture of 30% molecular oxygen and 70% elemental xenon according to feedback from the at least one carbon dioxide partial pressure sensor selected from the group consisting of the arterial blood carbon dioxide partial pressure sensor and the end tidal carbon dioxide partial pressure sensor, to maintain the arterial blood carbon dioxide partial pressure level between 41 and 65 mmHg.

9. 2. The system of claim 1, wherein the controllable mixing module controllably mixes a gas mixture of 5% carbon dioxide, 50% molecular oxygen, 45% elemental xenon and a gas mixture of 50% molecular oxygen and 50% elemental xenon according to feedback from the at least one carbon dioxide partial pressure sensor selected from the group consisting of the arterial blood carbon dioxide partial pressure sensor and the end tidal carbon dioxide partial pressure sensor, to maintain the arterial blood carbon dioxide partial pressure level between 41 and 65 mmHg.

10. 2. The system of claim 1, wherein the controllable mixing module controllably mixes a gas mixture of 5% carbon dioxide, 30% molecular oxygen, and 65% elemental argon with a gas mixture of 30% molecular oxygen and 70% elemental argon according to feedback from the at least one carbon dioxide partial pressure sensor selected from the group consisting of the arterial blood carbon dioxide partial pressure sensor and the end tidal carbon dioxide partial pressure sensor, to maintain the arterial blood carbon dioxide partial pressure level between 41 and 65 mmHg.

11. 2. The system of claim 1, wherein the controllable mixing module controllably mixes a gas mixture of 5% carbon dioxide, 50% molecular oxygen, and 45% chemical element argon with a gas mixture of 50% molecular carbon dioxide and 50% chemical element argon according to feedback from the at least one carbon dioxide partial pressure sensor selected from the group consisting of the arterial blood carbon dioxide partial pressure sensor and the end tidal carbon dioxide partial pressure sensor, to maintain the arterial blood carbon dioxide partial pressure level between 41 and 65 mmHg.

12. 1. A method for safely delivering an efficient amount of oxygen to a needed organ during cardiopulmonary resuscitation (CPR), comprising: (a) applying sequential distal-to-proximal compressive forces to the limb by compressing at least one limb device to occlude blood flow to said limb; (b) delivering the mixed gas by positive pressure ventilation; The step of feeding the mixed gas comprises: (I) providing a carbon dioxide enriched gas; (II) providing a molecular oxygen enriched gas; (III) controllably mixing the molecular oxygen enriched gas with the carbon dioxide enriched gas; (IV) detecting the partial pressure of carbon dioxide in arterial blood; (V) controlling at least one ratio selected from the group consisting of the ratio of the molecular oxygen enriched gas and the ratio of the carbon dioxide enriched gas in the mixed gas of the molecular oxygen enriched gas and the carbon dioxide enriched gas, The method further comprising: (c) providing an endotracheal tube including a sealing cuff disposed on a distal portion of the endotracheal tube; (d) providing the sealing cuff in a deployed configuration and engaging the sealing cuff with an inner surface of the trachea, thereby effectively sealing the passage of gas between the sealing cuff and the inner surface of the trachea while maintaining the flow of gas from the endotracheal tube into the trachea; (e) releasing the sealing cuff from the interior surface of the trachea while maintaining natural outflow of the gas from the trachea and applying a retention configuration to the sealing cuff; (f) performing myocardial stimulation on the myocardium to restore spontaneous circulation of the arterial blood by applying at least one stimulus selected from the group consisting of mechanical and electrical stimuli at predetermined time intervals; (g) continuously measuring the pressure within the trachea; (h) synchronizing timing of an inflation phase of the positive pressure ventilation system with the start of a depressurization phase of the cardiac stimulation.

13. The system of claim 1 , wherein the compression of the at least one limb device and the occlusion of blood flow to the limb is accomplished by an up-rolling contracting elastic ring.

14. 2. The system of claim 1, wherein the compression of the at least one limb device and the occlusion of blood flow to the limb is accomplished by applying at least one element selected from the group consisting of an elastic bandage, an elastic limb wrap with an adjustable closure, and an inflatable limb wrap with an adjustable closure.

15. 10. The system of claim 1, wherein the at least one limb device is configured to occlude arterial inflow of blood to the limb by applying a surface skin pressure range selected from the group consisting of 100-200 mmHg, 200-300 mmHg.

16. The mixed gas is 95% molecular oxygen and 5% carbon dioxide, 0.1-2.0% carbon dioxide, the rest molecular oxygen, 2.1-4.0% carbon dioxide, the remainder molecular oxygen, 4.1-5.6% carbon dioxide, the rest molecular oxygen, 0.1-5.0% carbon dioxide, 30-50% molecular oxygen, and the remainder the chemical element xenon.

2. The system of claim 1, wherein the gas is selected from the group consisting of 0.1-5.0% carbon dioxide, 30-50% molecular oxygen, and the remainder chemical element argon.

17. 10. The system of claim 1, further comprising: controllably mixing a gas mixture of 5% carbon dioxide and 95% molecular oxygen with pure 100% molecular oxygen according to feedback from the at least one carbon dioxide partial pressure sensor selected from the group consisting of the arterial blood carbon dioxide partial pressure sensor and the end tidal carbon dioxide partial pressure sensor, to maintain the arterial blood carbon dioxide partial pressure level at 41-45 mm.

18. 10. The system of claim 1, further comprising controllably mixing a hydrocarbon gas of 5% carbon dioxide and 95% molecular oxygen with pure 100% molecular oxygen according to feedback from the at least one carbon dioxide partial pressure sensor selected from the group consisting of the arterial blood carbon dioxide partial pressure sensor and the end tidal carbon dioxide partial pressure sensor, and maintaining the arterial blood carbon dioxide partial pressure level in at least one pressure range selected from the group consisting of 41-45 mmHg, 46-50 mmHg, 51-55 mmHg, and 56-65 mmHg.

19. 2. The system of claim 1, further comprising: controllably mixing a gas mixture of 5% carbon dioxide, 30% molecular oxygen, and 65% elemental xenon with a gas mixture of 30% molecular oxygen and 70% elemental xenon in accordance with feedback from the at least one carbon dioxide partial pressure sensor selected from the group consisting of the arterial blood carbon dioxide partial pressure sensor and the end tidal carbon dioxide partial pressure sensor to maintain the arterial blood carbon dioxide partial pressure level between 41-65 mm.

20. 2. The system of claim 1, further comprising: controllably mixing a gas mixture of 5% carbon dioxide, 50% molecular oxygen, and 45% elemental xenon with a gas mixture of 50% molecular oxygen and 50% elemental xenon in accordance with feedback from the at least one carbon dioxide partial pressure sensor selected from the group consisting of the arterial blood carbon dioxide partial pressure sensor and the end tidal carbon dioxide partial pressure sensor to maintain the arterial blood carbon dioxide partial pressure level between 41-65 mm.

21. 2. The system of claim 1, further comprising: controllably mixing a gas mixture of 5% carbon dioxide, 30% molecular oxygen, and 65% elemental argon with a gas mixture of 30% molecular oxygen and 70% elemental argon according to feedback from the at least one carbon dioxide partial pressure sensor selected from the group consisting of the arterial blood carbon dioxide partial pressure sensor and the end tidal carbon dioxide partial pressure sensor, to maintain the arterial blood carbon dioxide partial pressure level between 41-65 mm.

22. 2. The system of claim 1, further comprising controllably mixing a gas mixture of 5% carbon dioxide, 50% molecular oxygen, and 45% elemental argon with a gas mixture of 50% molecular oxygen and 50% elemental argon according to feedback from the at least one carbon dioxide partial pressure sensor selected from the group consisting of the arterial blood carbon dioxide partial pressure sensor and the end tidal carbon dioxide partial pressure sensor to maintain the arterial blood carbon dioxide partial pressure level between 41-65 mm.

23. 1. An endotracheal device for providing semi-voluntary positive pressure ventilation, comprising: (a) an elongate tube including an internal lumen and configured for intratracheal deployment; (b) a sealing cuff disposed on a distal portion of the elongate tube, the sealing cuff configured to repeatedly assume a deployed configuration and a retained configuration; (c) in the deployed configuration, the sealing cuff expands to engage an inner surface of the trachea, thereby effectively sealing a gas passageway between the sealing cuff and the inner surface of the trachea while maintaining the flow of gas from the endotracheal tube into the trachea; (d) an endotracheal device, wherein in the retained configuration, the sealing cuff is folded out of the way of the inner surface of the trachea while maintaining natural outflow of the gas from the trachea.

24. 24. The intratracheal device of claim 23, wherein the sealing cuff comprises an inflatable toroidal structure including an inflatable lumen.

25. 25. The endotracheal device of claim 24, further comprising at least one conduit connecting the inflatable lumen of the sealing cuff and the lumen of the elongate tube.

26. 25. The intratracheal device of claim 24, further comprising at least one outlet at a forward distal portion of the toroidal structure of the sealing cuff, configured to maintain flow of gas from the inflatable lumen of the sealing cuff into the trachea.

27. 24. The endotracheal device of claim 23, wherein the elongate tube comprises a one-way flow check valve configured to maintain flow of gas from the endotracheal tube into the trachea.

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