JP2012196483A - Resuscitation device and method for resuscitation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide stimulation means designed to provide resuscitating stimulation of the respiratory area of the human brain stem and induce aspiration reflex.SOLUTION: The resuscitation device for humans includes: a sensor for detecting parameter values in a human being; a memory for storing a predetermined function and detected parameter values; a processing unit connected with the sensor and the memory to determine whether the human being is in a state of developing apnea; and a response device connected with the processing unit for providing a response when the processing unit has determined that the human being is in the state of developing apnea. The resuscitation device is an apparatus including all of the sensor, the memory, the at least one processing unit and the response device, the apparatus is arranged to be attached under a human's nose, the sensor is arranged to sense breathing activity, and the response device induces stimulation in the nose philtrum of the human being. Resuscitating stimulation is preferably administered in the area of the nasopharynx enclosed by reference marks A, B, C, D surrounding the tuba auditiva 5.

Description

  According to a first aspect, the present invention relates to a device for inducing resuscitation in a human subject.

  According to a further aspect, the invention relates to a method for providing resuscitation therapy to a human subject in need thereof including, but not limited to, recovery of a life-threatening dysfunction.

  The brainstem contains multiple central mechanisms that coordinate multiple physiological life support functions. Impaired cardiopulmonary coordination can lead to multiple pathological conditions, some of which can be potentially life-threatening.

  Humans suffering from sleep apnea have cardiopulmonary disorders that appear with irregular breathing and even frequent respiratory arrest (apnea). This is noticeable during sleep but also occurs during the day. The risk of daytime apnea attacks is not very high. This is because seizures can be self-managed by conscious behavior. In the case of apnea during the night, the risk increases. Patients do not feel very good in daily life due to lack of oxygen. During an apneic attack, blood pressure may drop suddenly, followed by heart failure, resulting in inadequate brain perfusion, loss of consciousness, or even sudden death. Even. In developed countries, at least 4% of the adult population suffers from sleep apnea.

  There are several types of apnea. One type is central apnea, which involves dysfunction of respiratory muscles (including the diaphragm) due to lack of commands from the respiratory center in the brainstem. This is the type that occurs in about 10 percent of cases. Another type is obstructive apnea, which occurs in 80% of cases, where in spite of respiratory movement, the upper airway collapses due to strong negative inspiratory pressure. Air is not supplied to the lungs. The third type is mixed apnea, which occurs in the remaining patients.

It is known that apnea can be countered by stimulating the patient in various ways. For infants, usually just shaking can cause the infant to wake up from sleep, resume the process of automatic breathing, and even cause gasping, triggering resuscitation from suffocation. Adults suffering from sleep apnea currently sleep with a mask, connected closely to the contours of the face, thereby applying air continuously from the device at a slightly higher pressure (Continuous positive airway pressure-CPAP, Continuous Positive Airway Pressure). This keeps the airway open and allows air supply by spontaneous breathing. In any case, these patients need to be connected to a respiratory machine to sleep, limiting their freedom of movement during sleep. For patients with sleep apnea, travel means carrying a respiratory instrument.

Studies in cats have shown that stopping breathing by inhaling an anoxic mixture for more than 1 minute can subsequently significantly reduce blood pressure and heart rate. Mechanical or electrical stimulation of the pharyngeal nasal cavity can induce “sniff- and gasp-like“ suction reflexes ”(Z. Tomori and JGWiddicombe, Muscular, bronchomotor and cardiovascular reflexes elicited by mechanical stimulation of the respiratory tract, J. Physiol 200: 25-49,1969; R. Benacka and Z. Tomori, The sniff-like aspiration reflex evoked by electrical stimulation of the nasopharynx, Respir.Physiol.102: 163 -174, 1995; Z. Tomori, M. Kurpas, V. Donic and R. Benacka, Reflex reversal of apnoeic episodes by electrical stimulation of upper airway in cats, Respir. Physiol. 102: 175-185, 1995; Z. Tomori , R. Benacka and V. Donic, Mechanisms and clinicophysiological implications of the sniff- and gasp-like aspiration reflex, Respir. Physiol. 114: 83-98, 1998; Z. Tomori, R. Benacka,
V. Donic and J. Jakus, Contribution of upper airway reflexes to apnoea reversal, arousal, and resuscitation, Monaldi Arch. Chest Dis. 55: 398-403, 2000). The resuscitation effect restores blood pressure to normal, normalizes the heart rhythm, and restores normal breathing and neurobehavioral functions. Anesthetized cats appear to be in good condition even after 3 minutes without proper blood pressure, heart rate and respiration. This experiment can be repeated more than 10 times on the same cat without any noticeable negative results.

Inducing such aspiration reflex has been suggested as a possible means to interrupt apnea in cats (Tomori et al., 1991; Z. Tomori, M. Kurpas, V. Donic and
R. Benacka, Reflex reversal of apnoeic episodes by electrical stimulation of upper airway in cats, Respir.Physiol. 102: 175-185, 1995; R. Benacka and Z. Tomori, The sniff-like aspiration reflex evoked by electrical stimulation of the nasopharynx, Respir. Physiol. 102: 163-174, 1995; J. Jakus, Z. Tomori and A. Stransky, Neural determinants of breathing, coughing and related motor behaviors, Monograph, Wist, Martin, 2004). Alternatively, cats can induce similar resuscitation and induce convulsive inhalation by (electric) acupuncture, (electric) acupressure or mechanical stimulation in the nose (Benacka & Tomori, 1997 ).

  However, the typical convulsive inspiration of the suction reflex caused by the pharyngeal nasal cavity and pharyngeal oral cavity in cats is not noteworthy in humans, and this latter species is accompanied by a strong vomiting reflex This is the current view of existing technology (R. Benacka, Disorders of central regulation of breathing and their influencing by upper airway reflexes (in Slovak). Orbis Medince S; No .: 53-63, 2004). Other researchers have found a response in humans that is different from the aspiration reflex in response to stimulation of the upper respiratory tract using air pressure oscillating at high frequencies (Henke & Sullivan, 1992).

Z. Tomori and J. G. Widdicombe, Muscular, bronchomotor and cardiovascular reflexes elicited by mechanical stimulation of the respiratory tract, J. Physiol 200: 25-49,1969 R. Benacka and Z. Tomori, The sniff-like aspiration reflex evoked by electrical stimulation of the nasopharynx, Respir.Physiol. 102: 163-174, 1995 Z. Tomori, M. Kurpas, V. Donic and R. Benacka, Reflex reversal of apnoeic episodes by electrical stimulation of upper airway in cats, Respir. Physiol. 102: 175-185, 1995 Z. Tomori, R. Benacka and V. Donic, Mechanisms and clinicophysiological implications of the sniff- and gasp-like aspiration reflex, Respir. Physiol. 114: 83-98, 1998 Z. Tomori, R. Benacka, V. Donic and J. Jakus, Contribution of upper airway reflexes to apnoea reversal, arousal, and resuscitation, Monaldi Arch. Chest Dis. 55: 398-403, 2000 Tomori et al., 1991 J. Jakus, Z. Tomori and A. Stransky, Neural determinants of breathing, coughing and related motor behaviors, Monograph, Wist, Martin, 2004 Benacka & Tomori, 1997 R. Benacka, Disorders of central regulation of breathing and their influencing by upper airway reflexes (in Slovak) .Orbis Medince S; No .: 53-63, 2004 Henke & Sullivan, 1992

  Thus, in the prior art, nothing has been proposed in humans that provides resuscitation stimulation of the brainstem using induction of aspiration reflexes to obtain the physiological effects of resuscitation. There is also no commercially available device designed to treat apnea and related cardiorespiratory syndromes in humans through activation of the brainstem respiratory center and subsequent induction of the aspiration reflex.

  Here, surprisingly, the inventors of the present invention have found that, in humans, resuscitation stimulation of the respiratory region of the brainstem following induction of the aspiration reflex may result in central apnea and / or obstructive apnea, etc. It has been found that it has a beneficial effect on subjects suffering from or predisposed to several cardiorespiratory or neurobehavioral disorders of functional character, including apnea. This is not accompanied by any remarkable negative effects.

  The “suction reflex” causes a reset of brainstem control functions through strong activation of the respiratory center, which is thought to be similar to the activation of the brainstem center during automatic resuscitation triggered by gasping It has been. In the event of a rapid and powerful inspiratory actuation during gasping or an induced aspiration reflex, activation of the inspiratory center in the brainstem results in cardiac activity, blood pressure, and various neuropsychiatric and physical motor functions Other life-supporting centers, including the center that controls the life cycle, are reset. While not intending to be bound by any theory, it is believed that the present invention operates through the mechanism described for the following five groups of states.

  1) In patients with apnea and hypopnea caused by transient inactivation of inspiratory neurons in the brainstem, induction of aspiration reflex allows recovery from apnea and hypopnea, and spontaneous breathing It can be repaired. In patients with obstructive apnea, stimulation of the inspiratory center in the brainstem can restore airway closure and restore normal breathing.

2) In patients with transient ischemic attack (TIA), syncope, hypotension, migraine and hemorrhagic shock, the suction reflex activates the brainstem vasomotor center via the respiratory center Induces vasoconstriction and causes an increase in blood pressure, resulting in increased brain perfusion, disruption, termination, or at least relief of pathological conditions.

  3) Tremors in bronchospasm, laryngeal cramps, hiccups, epileptic seizures and Parkinson's disease can be inhibited by impulses through the reticulum from the inspiratory center. This impulse is transmitted through interneurons and has an inhibitory effect on the brainstem and other related control centers in the brain.

  4) In the case of alternating hemiplegia, sleep paralysis and absence epilepsy: stimulation via the inspiratory center and interneurons activates the descending part of the reticular body, which activates motor neurons End or at least alleviate the seizure.

  5) In the coma, depression, insomnia, Alzheimer's disease, anorexia nervosa, bulimia and autism, the ascending part of the reticular body is affected by stimulation via the inspiration center and interneurons. receive. This inhibits or reduces depression, bulimia, anorexia nervosa and improves concentration and other cognitive functions. This improves some coma, may inhibit the onset of Alzheimer's disease and autism, and positively affects insomnia and mental disorders.

  The benefits of resuscitation by stimulation of the brainstem respiratory center using induction of suction reflex for these conditions have not been previously identified in the prior art.

  The present invention seeks to provide a solution to the above drawbacks of the prior art.

For the purposes of the present invention, in one aspect, a resuscitation device is provided, the device comprising:
A plurality of sensing means for detecting several parameter values;
At least one storage means for storing a number of predetermined functions and possibly a number of detected parameter values;
At least one processing means connected to the sensing means and the storage means for processing the several detected parameter values in the predetermined function;
A number of response means coupled with the processing means for providing a response as a function of the plurality of processed parameter values. The device according to the invention is characterized in that several response means comprise several stimulation means designed to provide resuscitation stimulation of the respiratory region of the brainstem. It should be understood that resuscitation stimulation of brainstem inspiratory neurons means stimulation of the human body that triggers the aspiration reflex or its alternative, thereby affecting various brainstem centers . Through such stimulation, other parts of the brain that are relevant for conditions treatable with this device are affected. Suction reflex and its alternatives are common features that are powerful and short inspiratory actuation forces comparable to those that occur before or during one or more of gasping, air inhalation, sighing or increased breathing Have The stimulation of the inhalation region of the brain stem is preferably from a location far away from the brain stem.

The device according to the invention is suitable for inducing automatic resuscitation in a subject in need thereof. The term automatic resuscitation is observed in resuscitation by activation of compensatory natural mechanisms of human organisms through the inhalation of air and the induction of aspiration reflex near gasping, or in non-human animals and human infants It should be understood that it includes alternative forms in various species, similar to those brought about by automatic resuscitation by spontaneous gasping (Sridhar R., Thach BTet al .: Characterization of successful and failed autoresuscitation in human infants including those dying of SIDS. Pediatr. Pulmon. 36: 113-122, 2003; Xie J., Weil MH, Sun S., Yu T., Yang W .: Spontaneous gasping generates cardiac
output during cardiac arrest. Crit. Care Med. 32: 238-240, 2004). The term resuscitation can be used when referring to automatic resuscitation induction herein. Subjects who can benefit from the induction of automatic resuscitation include a) respiratory system, b) cardiovascular system, c) neurobehavioral changes, and d) hyperfunction of mental disorders, as discussed above. And subjects suffering from or having a predisposition to dysfunction such as functional decline. These include apnea, transient ischemic attack (TIA), bronchospasm associated with asthma, laryngeal cramps, hiccups, tremor associated with Parkinson's disease, seizures, absence epilepsy, migraine, hypotension, syncope , Bleeding shock (blood loss), alternating hemiplegia, Alzheimer's disease, depression, anorexia nervosa, bulimia, autism, mental disorder, sleep paralysis, insomnia, coma Is included.

  The sensing means may be any suitable means for detecting some parameter value. In this specification, unless stated otherwise, some shall mean one or more. The sensing means can provide an electrical output indicative of the determined parameter value in response to the determined parameter value. The determined parameter value is the value of the parameter measured / determined by the sensor within a specific time frame. The parameter may be any parameter that can determine whether the subject requires automatic resuscitation induction based on it.

  Suitable parameters for determining whether a subject needs resuscitation include, but are not limited to, a parameter corresponding to muscle activity, a parameter corresponding to respiration, or the electrical properties of neurons including brain cells. Includes parameters corresponding to brain activity such as activity or electrical activity recorded from the pharynx.

Parameters corresponding to muscle activity include, but are not limited to, muscle movement and electrical activity. Muscle movement can be detected by any sensing means suitable for detecting movement, such as a plurality of accelerometers. Muscle electrical activity is traditionally used to detect electromyogram (EMG), including electrocardiogram (ECG), electrocardiogram (ENG), actogram showing contraction, etc. Can be detected by the use of any suitable means known in the art, such as

  Parameters corresponding to breathing include, but are not limited to, muscles involved in respiratory activity such as the diaphragm, intercostal muscles, great pectoral muscles, abdominal muscles, upper and lower respiratory tract muscles, and other muscular activities involved Includes parameters. The parameters corresponding to the muscle activity discussed above are suitable. In an alternative embodiment of the device according to the invention, the parameter corresponding to the respiratory activity may comprise a gas flow in the airway and / or a gas flow near the inlet / outlet of the subject airway. It should be understood that the subject's airway entry / exit usually includes the nostril and / or mouth, or in some cases, the airway. Those skilled in the art are familiar with suitable means for determining gas flow, such as thermometers such as respiratory anemometers, or thermistors, Pt100, Pt1000 and others.

  In a further alternative embodiment of the device, the parameter corresponding to the respiratory activity may include sound. Sound is produced during breathing. Breathing sounds include, but are not limited to, snoring, inhalation and exhalation, and moaning. These sounds can be used to detect respiratory activity. Suitable sensing means for detecting sound include a microphone, a membrane connected to a coil / magnet system, or any other device capable of recording the movement or displacement of this membrane It is.

  Parameters corresponding to neural activity include, but are not limited to, electrical activity of neuronal cells or fibers, including brain cells (Neurogram-ENG). The electrical activity of the nerve cell can be any suitable known in the art, such as means conventionally used to detect electroencephalogram (EEG), such as measuring the potential difference between different locations on the scalp. Can be detected by the use of various means. It is also possible to measure changes in the magnetic fields resulting from electrical activity by recording current through coils placed in these magnetic fields. In general, various positions of the top of the skull are used, but the position of this application may also be the position under the base of the brain, the position in the oral nasal cavity. EEG activity can also be recorded from the pharynx, more specifically from the pharyngeal nasal cavity.

  A further method is by measuring the activity of the muscles that lead to eye movements (electrocardiogram-EOG, electrooculography). This is typically used, for example, to determine rapid eye movement (REM) sleep.

  The device according to the invention further comprises at least one storage means for storing a predetermined function and possibly several detected parameter values. The storage means may be any suitable storage means for storing a predetermined function, such as a computer readable memory. The predetermined function may be a mathematical function or a correlation. An appropriate function may be a function suitable for determining whether the determined parameter value is equal to, greater than, or less than a predetermined threshold value. A person skilled in the art can determine an appropriate function based on his knowledge. Based on the appropriate function, a response is required as a function of the determined parameter value. For example, the function may relate to the absence of a particular parameter value below a particular threshold for a particular time frame. Such a function can be determined to detect the absence of respiration for a particular period of time, eg, 5 seconds or more or 10 seconds or more.

  In a preferred embodiment of the invention, the plurality of storage means are suitable for storing a number of detected parameter values. A person skilled in the art can select suitable storage means for storing the detected parameter values. A computer readable storage means may be suitable.

  The apparatus according to the invention further comprises at least one processing means connected to the sensing means and the storage means for processing the several detected parameter values in the predetermined function. The processing means may be a microprocessor. In the processing means, the parameter value detected by the sensing means is processed in a predetermined function. For this, whether the detected parameter value is read directly from the sensing means in the processing means or alternatively from the storage means from which the detected parameter value was previously read. Either. The predetermined function is read from the storage means into the processing means, or in an alternative embodiment, the predetermined function can be embedded in the processing means. In the latter embodiment, the at least one storage means can be (partially) integrated in the processing means.

The apparatus further includes a number of response means connected to the processing means for providing a response as a function of the number of processed parameter values. The several response means include a plurality of stimulation means designed to provide a resuscitation stimulus to stimulate and / or reactivate the inspiratory center of the brainstem. In non-human animals, the inhalation center of the brainstem is stimulated directly using microelectrodes inserted into the outer capsular area of the medulla, and convulsive inhalation close to air inhalation, gasping and hiccups (Batsel HL, Lines AJ: Bulbar respiratory neurons participating in the sniff reflex in the cat, J. Exper. Neurol 39: 469-481, 1973; St John WM, Bledsoe TA, Sokol HW: Identification of medullary loci critical for neurogenesis of gasping J. Appl. Physiol. 56: 1008-1019, 1984; St John et al., 1996; Arita H., Oshima T., Kita I., Sakamoto M .: Generation of hiccup by electrical stimulation in medulla of cats. Neurosci. Lett. 175: 67-70, 1994). Alternatively, the inspiration center can be activated indirectly by stimulation at a location remote from the brainstem. Preferred primary stimuli travel from the upper respiratory tract, preferably the pharynx, to the inhalation center in the brainstem. In the brainstem there are other control centers such as vasomotor centers and nerve cells that control heart activity, which are also secondarily affected as a result of stimulation of the inspiration center. Furthermore, the inspiration center is connected to a reticulated body (RF) by interneurons. The descending part of the RF connects to the peripheral nervous system, such as various motor and sensory neurons; the ascending part, for example, connects to higher centers that control sensory, sensory and cognitive functions .

  Resuscitation is triggered by stimuli at specific locations far from the brainstem. This is because at certain locations in the mammalian body, there are afferent nerves connected to the inhalation center of the brainstem. Stimulating such afferent nerves or their receptive zones activates the inspiratory center of the brainstem, through which other centers in the brainstem and other parts of the brain are affected, resulting in resuscitation and / Or can trigger automatic resuscitation.

  The resuscitation stimulation of the inhalation center of the brainstem is preferably performed at a location far from the inhalation center. Examples of such areas are the upper respiratory tract, preferably the pharynx, the pharyngeal acupuncture points GV26 in the nose and the acupuncture points on the ear pinna. Stimulation of the pharyngeal nasal cavity, more preferably the part of the pharyngeal nasal cavity near the ear canal is preferred. This is because the induction of suction reflexes provides the most powerful resuscitation effect.

  The stimulation means may be an electrical stimulation means. The electrical stimulation means may include a power source and / or a wave generator. When combined with an appropriate power source, the wave generator can generate block waves, sine waves and spikes of different lengths, frequencies and amplitudes.

  The electrical stimulation means may further include an electrode for delivering electrical stimulation to the subject's body. The electrodes may be monopolar or multipolar, including bipolar electrodes, or may be placed on the surface of the body or firmly fixed in various tissues of the subject's body. To stimulate the acupoint GV26 on the nose and the acupuncture points on the ear pinna, electrodes can be placed on the skin. Alternatively, the electrode may have the form of a needle that at least partially penetrates the subject's skin. To stimulate the pharynx, the electrode can be securely fixed to the subject's pharynx.

In a preferred embodiment, multiple stimulation electrodes and several collection electrodes are used. By using several stimulation electrodes, more complex stimulation currents can be provided. This also allows the region to be stimulated to be more accurately defined. When several electrodes are used, it is preferable that there is some distance between the electrodes. Because of this distance, current travels through that distance through the subject's body. This enhances the stimulation effect. In cardiac pacemakers, spike stimulation is used (eg, 1.2V, 20 milliseconds). Apart from a series of spikes over a long period (several seconds), the amplitude and duration of the spikes, ie the amount of energy, can be varied (R. Benacka and Z. Tomori, The sniff-like aspiration reflex evoked by electrical stimulation of the nasopharynx, Respir. Physiol. 102: 163-174, 1995). Various frequencies and durations of sine waves, block waves, spikes, spike trains, and any combination thereof can be used. Rather than simply transferring energy, it is preferable to more complex stimulate the target response center to elicit the desired physiological response.

  The electrical stimulation lead is firmly secured to the selected area of the subject's body by securing means. Any suitable securing means known in the art for securely securing electrical stimulation leads to a mammalian body, including the human body, is suitable. A suitable example is a tread of a screw that can be used to screw an electrical stimulation lead into a selected tissue, such as a muscle. An alternative fixation means is a flav that grows into the muscle (for example, four parts in the form of a cross at the end of the electrode) or sewing.

  For stimulation of the pinna of the ear pinna, electrical stimulation means can be designed, for example, in a P-stim® device manufactured by E. Siegler GmbH (Austria).

  In an alternative embodiment, the stimulation means is a mechanical stimulation means. The mechanical stimulation means is suitable for stimulating mechanoreceptors in the dorsal lateral region of the pharyngeal nasal cavity, acupuncture points GV26 in the nose and the acupoints on the ear pinna. Mechanical stimulation means are suitable means for touching or applying pressure to these parts of the subject's body using stretchable nylon fibers and thin polyvinyl catheters. Mechanical stimulation can also be provided by means of a gas pressure pulse. Other suitable means for providing mechanical pressure include heel, acupressure, electrical acupressure (a combination of mechanical and electrical stimulation).

  In an alternative embodiment, the stimulation means is a chemical stimulation means. Chemical stimulation means are suitable for stimulating the upper airway innervated by the trigeminal, olfactory and glossopharyngeal nerves. Multiple chemical stimuli have been found to induce arousal responses and some degree of resuscitation by stimulating chemoreceptors in the upper respiratory tract. These receptors, among other things, are involved in olfactory detection, causing a short-term increased inspiratory actuation force (air inhalation) to change the direction of air flow with odorous substances to the olfactory region of the upper respiratory tract, Detect and identify odorous substances. Chemical irritation can be triggered by contacting the upper respiratory tract with a chemical composition that induces resuscitation. The chemical composition is preferably in the form of a gas or aerosol when in contact with the pharynx. Many odors result from the mixing of compounds.

  Chemical induction of resuscitation can be effected by a trigeminal-olfactory stimulant comprising, for example, one or more of vanillin, amyl acetate, propionic acid or phenylethyl alcohol. However, it is clearly stated that the present invention is not limited to chemical stimulation with these odors / compounds.

  In order to dispense the chemical composition, the chemical stimulation means can include a spraying means. The spraying means may be appropriate when spraying (pressurized) gas and / or spraying liquid (including atomizing). Suitable spraying means are known to those skilled in the art. The spraying means is suitable for spraying the chemical composition in the vicinity of the subject's nose and / or mouth. In this way, the subject can inhale the odorous composition through the nose, so that the pharyngeal mucosa can be chemically stimulated by components of the chemical composition.

  The device according to the invention is, in a preferred embodiment, at least partially implantable in the human body. This device is preferably fully implantable in the human body. Implantation is particularly suitable when using electrical and / or mechanical stimulation means.

  This complete implantation of the device makes it easier for the subject to use the device because there are no parts on the surface of the subject's body. The implanted device can serve as an alternative to a positive pressure supply device that prevents airway obstruction. It is known from the cardiac pacemaker that the battery life is as long as 10 years. In the case of the presented device, it can be expected that the battery life will be much longer. Or the device may be made much smaller. This is because the device does not need to be stimulated as often as a cardiac pacemaker. In a cardiac pacemaker, about 70% of the pacemaker's volume is occupied by batteries and connectors.

  The implantable device according to the present invention can be designed such that the device does not include any detection or stimulation leads externally. Such a device can use a conductive housing as an antenna to detect electrical activity in the human body, eg, to detect EEG. An electrically conductive housing can be used as well to direct current to the immediate part of the human body. Such devices can be applied to electrical stimuli, implanted in parts of the human body and used to induce resuscitation stimulation in the respiratory region of the brainstem, for example using induction of aspiration reflexes in the pharyngeal nasal region. Obtainable.

  In a different embodiment, the device according to the invention is suitable for being worn on or behind a mammalian ear, preferably a human ear. Several devices for wearing on the human ear are known in modern life, such as (wireless) audio headsets for (mobile) telephones and various music players. A further example of a device worn behind the ear is the P-stim® device manufactured by E. Biegler GmbH (Austria). A person skilled in the art has the concept of wearing a device including a battery and (microminiature) electronics on a human ear, as used in these headsets and P-stim® devices. It will be understood how it should be used in the device according to the invention.

According to a further aspect, the present invention relates to a method for providing resuscitation therapy to a subject in need thereof, including restoration of life-threatening dysfunction and normalization of associated life support functions. The method according to the invention comprises:
Monitoring whether the subject requires resuscitation or elimination or mitigation of dysfunction; and
Providing a resuscitation stimulus in the respiratory region of the subject's brainstem, preferably at a location remote from the respiratory region;
Secondarily affecting the regulation mechanisms of other life support functions that support their normalization.

  Subject monitoring may be in various forms known to those skilled in the art. Several possible ways to monitor that a subject needs resuscitation have already been discussed above.

  A preferred embodiment of the method of the present invention relates to a method for stimulating a respiratory region of a subject's brainstem. Stimulation is preferably performed at a location far away from the subject's breathing region (or better). According to the present invention, a suitable place for resuscitation stimulation is the pharynx, preferably the pharyngeal oral cavity, more preferably the pharyngeal nasal cavity, most preferably the pharyngeal nasal cavity area around the ear canal.

  Alternatively, the resuscitation stimulus can be provided by a stimulus in the nose, preferably by stimulation of the acupoint GV26.

  In a further alternative embodiment of the invention, the resuscitation stimulus is provided by stimulation of the acupuncture points on the pinna of the ear.

  Resuscitation or normalization stimulation can be effected using any means suitable for providing resuscitation stimulation of the respiratory center of the human brainstem. According to a preferred embodiment of the method according to the invention, electrical stimulation, mechanical stimulation or chemical stimulation is used. Most preferred is the use of electrical stimulation. Appropriate means of providing resuscitation stimuli have been discussed above.

  Methods according to the present invention include, but are not limited to, apnea such as central or obstructive apnea, transient ischemic stroke (TIA), hypotension, syncope, hemorrhagic shock (blood Loss), bronchospasm, laryngeal spasm, hiccup, tremor associated with Parkinson's disease, seizures, absence epilepsy, migraine, alternating hemiplegia, Alzheimer's disease, depression, anorexia nervosa, bulimia, self Suitable for treatment of one or more of autism, mental disorder, insomnia, sleep paralysis, and coma. As used herein, the term treatment should be construed to encompass or provide relief from the discomfort of life-threatening dysfunction.

  The invention will now be further illustrated with reference to the following examples and the accompanying figures.

It is a schematic cross-sectional view of a part of a human head and neck. It is a figure which shows the detail from FIG. 3 to 5 are diagrams showing polysomnographic data of a human adult suffering from sleep apnea. 3 to 5 are diagrams showing polysomnographic data of a human adult suffering from sleep apnea. 3 to 5 are diagrams showing polysomnographic data of a human adult suffering from sleep apnea. 3 to 5 are diagrams showing polysomnographic data of a human adult suffering from sleep apnea. 3 to 5 are diagrams showing polysomnographic data of a human adult suffering from sleep apnea. 3 to 5 are diagrams showing polysomnographic data of a human adult suffering from sleep apnea.

  As shown in FIG. 1, the pharynx is positioned from the underside of the skull to the level of the cervical vertebra C6. The pharynx is divided into three compartments: the pharyngeal nasal cavity (positioned approximately behind the nasal cavity, between arrows 1 and 2), the pharyngeal oral cavity (positioned approximately behind the oral cavity, between arrows 2 and 3), and It can be divided into the pharyngeal larynx (between arrows 3 and 4, which is located approximately behind the larynx). FIG. 2 shows a preferred location for pharyngeal resuscitation stimulation. The resuscitation stimulus is preferably applied in the pharyngeal nasal cavity region surrounded by reference symbols A, B, C, D around the ear canal 5. More preferably, the resuscitation stimulus is applied in the immediate vicinity of the ear canal 5 indicated by the oblique lines in FIG.

Experimental example 1
Moderate mixed sleep apnea (RDI, Respiratory Disturbance Index = 35 / hour) and excessive daytime sleepiness (Epword Sleepiness Scale (ESS) score, 15 to 24) Patients with J. M, 55 years old, male was examined (polysomnography overnight and continuous positive airway pressure-CPAP test) and the following parameters were recorded continuously.
LEOG and REOG-left and right electrooculogram (eye movement)
C4A1 and C3A2-electroencephalogram-EEG (brain action potential)
1. EMG-electromyogram-muscle action potential MICRO-recording of breathing sound (snoring) with microphone NAF-air flow through nose with thermistor THO-chest movement with tensiometer ECG = electrocardiogram Heart rate [/ min] from lead RR-ECG.
SAO2-arterial blood oxygen saturation [%]
LITE-ambient light intensity [%]
Time-experimental change in experiment STAGE-non-REM sleep stage 2: S2
The results of this experiment are shown in FIGS. 3A-3B and discussed below.

FIG. 3A. Central sleep apnea lasting about 23 seconds (both chest movements and airflow cease), bradycardia (heart rate decreased from 51-53 / min to 48-50 / min, about 15 seconds With a delay, the O ₂ saturation decreased from 93% to 88%). Later, spontaneous breathing gradually resumed, accompanied by snoring, hyperventilation and tachycardia (65 / min).

FIG. 3B. In non-REM sleep phase 2, the occurrence of two short seizures lasting 8 and 9 seconds of central sleep apnea is interrupted by GV26 electrical acupuncture stimulation, close to chest movements and short inhalation of air Rapidly inspiring inspiratory air flow with sound resulted in spontaneous breathing, but without hyperventilation, snoring and significant changes in heart rate and O ₂ saturation. Note that ECG and RR values from about 37 seconds to 40 seconds do not correspond to the physiological values of the subject. Instead, during this time, ECG and RR measurements are disturbed by electrical stimulation. Activation of brainstem inspiratory neuronal reflexes via acupoint GV26 was suitable for recovery from central sleep apnea.

Experimental example 2
Patients with severe mixed sleep apnea (RDI = 48 / hour) S, 51 years old, male was examined (overnight polysomnograph) and the following parameters were recorded continuously.
LEOG and REOG-left and right electrooculogram (eye movement)
C4A1 and C3A2-electroencephalogram-EEG (brain action potential)
1. EMG-electromyogram-muscle action potential MICRO-recording of breathing sound (snoring) with microphone NAF-air flow through the nose with thermistor THO-chest movement with tensiometer-ECG-electrocardiogram Heart rate [/ min] from lead RR-ECG.
SAO2-arterial blood oxygen saturation [%]
LITE-ambient light intensity [%]
Time-time course in experiment STAGE-Non-REM sleep stage 1: S1; stage 2: S2
The results of this experiment are shown in FIGS. 4A-4B and discussed below.

FIG. 4A. Obstructive sleep apnea lasting about 46 seconds (air flow stops despite strong sustained chest movements), bradycardia (heart rate decreased from 53 / min to 44 / min, With some delay, the O ₂ saturation decreased from 93% to 81%). Later, spontaneous breathing gradually resumed, accompanied by snoring, hyperventilation and increased heart rate (70 / min). Note that the ECG, RR, C4A1 and C3A2 values from about 60 to 78 seconds do not correspond to the subject's physiological values. Instead, during this time, ECG, RR, C4A1 and C3A2 measurements are disturbed by excessive chest movements and strong EMG.

FIG. 4B. In non-REM sleep stage 1, the occurrence of an obstructive sleep apnea attack lasts 7 seconds and is then interrupted by gently mechanically touching the pharyngeal nasal mucosa with elastic nylon fiber, Rapidly inspiring air flow with a sound close to the movement of the air and short air inspiration followed by spontaneous breathing, but significant changes in heart rate and O ₂ saturation were It was not accompanied. Activation of brainstem inspiratory neuron reflexes using contact stimulation of the pharyngeal nasal cavity was suitable for recovery from obstructive sleep apnea.

Experimental example 3
Patients with moderate central sleep apnea (RDI = 32 / hour) H, 56 years old, male was examined (overnight polysomnograph) and the following parameters were recorded continuously.
LEOG and REOG-left and right electrooculogram (eye movement)
C4A1 and C3A2-electroencephalogram-EEG (brain action potential)
EMG-Electromyogram-Muscle action potential MICRO-Recording of breathing sound (snoring) by microphone NAF-Air flow through nose by thermistor THO-Chest movement by tensiometer ECG-Heart rate from ECG RR-ECG [ / Min] is not shown for technical reasons.
SAO2-arterial blood oxygen saturation [%]
LITE-ambient light intensity [%]
Time-time course in experiment STAGE-Non-REM sleep stage 1: S1; stage 2: S2
The results of this experiment are shown in FIGS. 5A-5B and discussed below.

FIG. 5A. In non-REM sleep stage 1, the period of hyperpnea lasting about 25 seconds (middle of the figure) precedes, followed by two episodes of hypopnea, suggesting unstable sleep in the supine position. Changes in breathing patterns reflect periodic changes in arterial O ₂ saturation between 91%, 87% and 94%, delayed 15-20 seconds. Due to technical problems, the ECG and heart rate (RR) recordings of FIGS. 5A and 5B do not show the actual physiological values of the subject.

FIG. 5B. In non-REM sleep stage 2, the occurrence of a central sleep apnea attack lasts 8 seconds and is then interrupted by gently mechanically touching the pharyngeal nasal mucosa with elastic nylon fibers (arrows) Inspired air flow rapidly with sound similar to chest movements and short air inhalations. This was followed by spontaneous breathing, but without a significant change in O ₂ saturation (from 90% to 88% to 91%). Activation of brainstem inspiratory neuron reflexes with contact stimulation of the pharyngeal nasal cavity was suitable for recovery from a central sleep apnea attack.

From the results presented, both GV26 electrical acupuncture (FIGS. 3A-3B) and mild mechanical stimulation of the pharyngeal nasal mucosa (FIGS. 4A-4B and 5A-5B) are both central and obstructive in human adults. It has been demonstrated that sexual sleep apnea attacks can be interrupted to prevent the occurrence of significant changes in heart rate and O ₂ saturation and to resume spontaneous breathing.

  The implantable device includes a stainless steel or titanium casing. Surrounded within the casing are batteries (typically lithium iodide with nanocrystalline positive electrode components as used in cardiac pacemakers) and microelectronics. The microelectronic device includes a system for recording an electromyogram (EMG) detected by a detection electrode connected to the device. The detection electrode is suitable for attachment to the diaphragm. EMG data (repetition of intensity, frequency, phase activity) is processed in a microprocessor. Microprocessors can detect EMG if there is no normal EMG activity for> 10 seconds (central apnea) or extremely strong EMG activity with airflow cessation (obstructive apnea) It is designed to activate the wave function generator if it does not meet the predetermined criteria. When the wave function generator is activated, it generates a predetermined wave, such as a sine wave, block wave, spike train or any combination of the appropriate frequency, duration and amplitude, Through the electrical wire of the mechanical stimulation lead to the stimulation electrode. The electrical stimulation lead is suitable for being firmly fixed in the dorsal outer region of the pharyngeal nasal cavity.

Another device of the present invention is based on stimulation of the upper respiratory tract by chemical stimulation. The electronic device can be attached near the head of the sleeping subject. The device monitors the patient's breathing by monitoring sound using a microphone or by monitoring air flow using a flow meter. When an apneic attack occurs, the device releases the appropriate chemical composition from the reservoir by means of nebulization to stimulate the upper airway mucosa. This induces air inhalation and resuscitation in the subject. Resuscitation normalizes respiration, blood pressure and heart rate. The chemical composition in the reservoir can be exchanged. This facilitates refilling and allows the chemical composition to be exchanged for other compositions. Exchange with different chemical compositions prevents the loss of response due to adaptation. The device can also include several reservoirs with different chemicals, allowing for randomization. Such a device can also be used to assist in preventing sudden infant death (SID). The advantage of this method is that no treatment occurs without an apnea attack.

  There are also other ways to reactivate and cause resuscitation to the brainstem centers that control life-sustaining functions. One example is an electrical or mechanical stimulation of the acupoint GV26 in the nose. This is provided by an instrument attached under the patient's nose to monitor breathing by detecting airflow with a flow meter and to stimulate the acupoint GV26 under the nose during an apneic attack Can do.

  Another example is acupuncture stimulation on the ear pinna. Finding the location of these points accurately is difficult, but once found, these points can be stimulated to obtain a reflex effect similar to stimulation of the pharyngeal nasal cavity or nasal filter. An electronic “ear cap” that monitors the patient's breathing, for example, by breathing sounds and provides stimulation during an apneic attack will help the patient.

  It should be understood that the embodiments presented in the above examples are merely illustrative of the invention and are not intended to limit the scope of the invention.

(References)

Claims (6)

A sensor for detecting several parameter values in humans;
At least one memory for storing a predetermined function and a number of detected parameter values;
The sensor and the memory for processing the number of detected parameter values in the predetermined function to determine whether the person is in a state of developing apnea; At least one connected processing unit;
If the at least one processing unit determines that the human is in a state of developing apnea, a response as a function of the several parameter values processed by the at least one processing unit. A resuscitation device for humans, comprising a responding device connected to the processing unit for providing,
The resuscitation device is an instrument including all of the sensor, the memory, the at least one processing unit and the response device, the instrument being arranged to connect under a human nose; A stimulator arranged to detect respiratory activity and wherein the responder is designed to induce aspiration reflex by resuscitation stimulation of the respiratory region of the human brainstem by causing stimulation in the human nose The apparatus characterized by including. The device of claim 1, wherein the stimulator is designed to cause induction of aspiration reflex by stimulating the acupuncture point GV26 above the human nose. The apparatus according to claim 1 or 2, wherein the sensor is arranged to sense at least one of gas flow, gas composition, gas pressure, gas temperature, body temperature and sound. The device according to claim 1, wherein the response device is at least one of an electrical response device and a mechanical response device. The apparatus of claim 4, wherein the stimulator comprises a unit for providing at least one of electrical stimulation, gas pressure pulses, sputum, finger pressure, electric sputum and electric finger pressure. 6. The device of claim 5, wherein the stimulation device comprises an electrode arranged to be placed on the human skin.