JP2006288568A - Device for simultaneously controlling intracranial pressure and brain temperature and its controlling method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a device which enables a worker with less experience to control an intracranial pressure and a brain temperature safely and simultaneously by adjusting the intracranial pressure of a homeotherm in a desired pressure region promptly and accurately and simultaneously keeping the brain temperature in a safe temperature region all the time, and its controlling method. <P>SOLUTION: The device is equipped with an intracranial pressure sensor 12 and a brain temperature sensor 14 for respectively measuring the intracranial pressure and the brain temperature of the homeotherm 1, a cooling device 20 for cooling a body of the homeotherm at a prescribed cooling temperature T, and a control device 30 for controlling the cooling temperature T from the measured intracranial pressure and brain temperature. The control device 30 is equipped with a storage device for storing safe regions of the intracranial pressure and the brain temperature and each reference value of a gain of the intracranial pressure by a change in a body temperature, of a time constant, and of a dead time, and sets a control coefficient of the cooling temperature T from each reference value and controls the setting to make the intracranial pressure reach a target value by sufficiently suppressing the overshoot of the intracranial pressure and the brain temperature. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a simultaneous control device for intracranial pressure and brain temperature and a control method thereof for managing intracranial pressure and brain temperature due to increased intracranial pressure in a head injury patient within a safe range.

Intracranial hypertension is a symptom of abnormally increased intracranial pressure, and is one of the most common complications after surgery for head trauma patients. If this intracranial hypertension progresses, it may cause cerebral ischemia and cerebral hernia, which may worsen the patient prognosis. For this reason, intracranial hypertension is regarded as very important in the clinical field of neurosurgery, and stable control of intracranial pressure is the basis for treatment of brain disorders and postoperative management.

As means for lowering the intracranial pressure, cerebral cryotherapy is known in addition to head elevation, osmotic diuresis, hyperventilation therapy, cerebrospinal fluid induction, decompression craniotomy, and the like. Brain hypothermia has been shown to be effective in intractable intracranial hypertension, and is sometimes the last choice (therapeutic tool). Such cerebral cryotherapy is disclosed in Non-Patent Document 1, for example.

Moreover, the measuring means of the intracranial pressure is disclosed in Patent Documents 1 to 3, and the body temperature holding device for small animals related to the present invention is disclosed in Patent Document 4.

As shown in FIG. 11, the “intracranial pressure detecting device” of Patent Document 1 is attached to a mounting body 51 that is detachably mounted on the head of a human body as a subject, and is attached to the inside of the mounting body. The pressure receiving body 52 that changes the pressure of the sealed air in accordance with the fluctuation of the pressure inside the skull when the mounting body is sealed to the head of the mounting body, and the change in the air pressure inside the pressure receiving body And a pressure detector 55 that detects and outputs an electrical signal.

As shown in FIG. 12, the “intracranial pressure gauge” of Patent Document 2 takes cerebrospinal fluid out of the scalp 63 through a shunt path 60 that is provided under the scalp 63 and drains cerebrospinal fluid from the ventricle 62. A needle-shaped pipe 64 and a detector 65 for introducing cerebrospinal fluid taken out by the needle-shaped pipe and measuring the intracranial pressure are provided.

The “method and apparatus for measuring, monitoring or detecting intracranial pressure” of Patent Document 3 is a pressure detection diaphragm provided at the tip, side surface, or a plurality of positions of a magnetic resonance compatible catheter 72 shown in FIG. Magnetic resonance-compatible microsensor pressure transducer coupled to the lateral ventricle, cerebral cistern, subarachnoid space, subdural or epidural space, venous sinus, or intraparenchymal tissue location by magnetic resonance imaging guidance And the intracranial pressure is recorded.

As shown in FIG. 14, the “body temperature maintaining device for small animals” of Patent Document 4 includes a heater device 85 having a heater heating element 81 that heats a flat surface on which a small animal is mounted without temperature unevenness, and a central surface of the heater device. And a heater control device that detects the temperature of the abdomen of a small animal that is in contact with the surface of the heater device and maintains the set temperature at the same time.

Edited by Tatsujun Arai, “Brain Resuscitation and Hypothermia Therapy”, Shinko Trading Medical Book Publishing Department, revised in August 2000

JP-A-8-84704, “Intracranial Pressure Detection Device” Japanese Patent Laid-Open No. 10-276993, “Intracranial Pressure Gauge” JP 2001-346767, “Method and apparatus for measuring, monitoring or detecting intracranial pressure” JP 2002-51662 A, “Body temperature holding device for small animals”

As described above, cerebral cryotherapy has been recognized as effective for intractable intracranial hypertension, but has the following problems.
(1) In the management of intracranial pressure by conventional cerebral hypothermia, a medical worker manually adjusts the cooling temperature based on experience. However, since intracranial pressure is affected by brain temperature, body temperature, metabolism (water production and heat production), diuretics, anesthetics, etc., it is difficult for an expert to manage the intracranial pressure empirically. It was.
(2) Even if the patient's body temperature is kept low, the delay time of the decrease in intracranial pressure is very long (for example, usually 8 hours or more), so medical personnel monitor body temperature and intracranial pressure for a long time. It was necessary to continue, and the burden on the medical staff was very heavy.
(3) Furthermore, when the brain temperature falls below 33 ° C., it induces a decrease in cardiac function and arrhythmia. Therefore, if the body temperature is rapidly lowered to reduce the intracranial pressure, the brain temperature causes cardiac dysfunction and the like. The following dangerous temperatures may be reached.
(4) In addition, in order to establish the cause and treatment method of such intracranial hypertension, control of intracranial pressure using experimental animals is indispensable. Conventionally, the body temperature of experimental animals must be accurately adjusted. Therefore, it has been extremely difficult to verify the therapeutic effect of hyperthermia by intracerebral hypothermia using experimental animals.

  The present invention has been developed to solve the above-described problems. That is, the object of the present invention is to accurately and quickly adjust the intracranial pressure of a thermostatic animal (human or laboratory animal) to a desired pressure range, and at the same time, it is possible to always keep the brain temperature within a safe temperature range. Accordingly, it is an object of the present invention to provide a device and a control method thereof that can control the intracranial pressure and the brain temperature simultaneously and safely even by a less experienced worker.

According to the present invention, an intracranial pressure sensor and a brain temperature sensor for measuring an intracranial pressure and a brain temperature of a thermostatic animal,
A cooling device for cooling the body of the constant temperature animal at a predetermined cooling temperature T;
A control device for controlling the cooling temperature T based on the measured intracranial pressure and brain temperature,
The control device includes a storage device for storing the reference values of the safe range of the intracranial pressure and brain temperature, the gain of the intracranial pressure due to body temperature change, the time constant, and the dead time,
The intracranial pressure and the brain are controlled by setting a control coefficient of the cooling temperature T from each of the reference values so that the overshoot of the intracranial pressure and the brain temperature is sufficiently reduced by the control device to reach the target value. A simultaneous temperature control device is provided.

According to a preferred embodiment of the present invention, the control coefficients are a proportional coefficient K _P , an integral coefficient K _I and a differential coefficient K _D of the cooling temperature T due to a difference e between the target value and the measured value of the intracranial pressure P,
The control device performs PID feedback control of the cooling temperature T using the proportional coefficient K _P , the integral coefficient K _I and the differential coefficient K _D of the cooling temperature T obtained from the respective reference values.

Further, the control device corrects the proportional coefficient K _P , the integral coefficient K _I, and the differential coefficient K _D of the cooling temperature T obtained from each reference value based on the difference e between the target value and the measured value of the intracranial pressure P. It has a correction calculation function.

In addition, it has a blood temperature sensor that measures the blood temperature supplied to the brain of a constant temperature animal,
The control device controls the cooling temperature T of the cooling device so that the measured blood temperature is equal to or higher than the lowest temperature in the safe range of brain temperature.

  The cooling device includes an enclosure that surrounds the body of a constant temperature animal, a refrigerant supply device that supplies a cooling medium into the enclosure, and a medium cooler that cools and holds the temperature of the cooling medium to a predetermined cooling temperature T. Become.

  In addition, the cooling device includes a cooling plate on which a body of a constant temperature animal is placed, a cooling Peltier element that contacts a part of the lower surface of the cooling plate and cools the cooling plate, and contacts and cools a part of the lower surface of the cooling plate. It is preferable to include a heating Peltier element that heats the plate, and a cooling control device that supplies a current to the cooling Peltier element or the heating Peltier element and cools and maintains the temperature of the cooling plate at a predetermined cooling temperature T.

Further, according to the present invention, control of an apparatus including an intracranial pressure sensor and a brain temperature sensor that respectively measure the intracranial pressure and brain temperature of a thermostat animal, and a cooling device that cools the body of the thermostat animal at a predetermined cooling temperature T. A method,
A storage step for storing each of the reference values of the safe range of the intracranial pressure and brain temperature, the gain of the intracranial pressure due to a change in body temperature, the time constant, and the dead time;
A setting step for setting a control coefficient of the cooling temperature T from each of the reference values so as to reach the target value while suppressing the overshoot of the intracranial pressure and the brain temperature sufficiently;
A control step of controlling the cooling temperature T by using the set control coefficient based on the intracranial pressure and the brain temperature measured by the intracranial pressure sensor and the brain temperature sensor. A method for simultaneous temperature control is provided.

According to a preferred embodiment of the present invention, in the setting step, the proportional coefficient K _P , the integral coefficient K _I, and the derivative of the cooling temperature T according to the difference e between the target value and the measured value of the intracranial pressure P from the reference values. set the coefficient _{K D,}
In the control step, the proportional coefficient K _P is _set, the cooling temperature T for PID feedback control using the integral coefficient K _I and the differential coefficient K _D.

Also it has a step of correcting the proportional coefficient K _P, the integral coefficient K _I and the differential coefficient K _D of the cooling temperature T based on the difference e between the measured value and the target value of the intracranial pressure P, determined from the respective reference value .

Also equipped with a blood temperature sensor that measures the temperature of blood supplied to the brain of a constant temperature animal,
In the control step, it is preferable to control the cooling temperature T of the cooling device so that the measured blood temperature is equal to or higher than the lowest temperature in the safe range of the brain temperature.

  According to the apparatus and method of the present invention, the gain of the intracranial pressure due to a change in body temperature, and the time so that the overshoot of the intracranial pressure and brain temperature of a thermostatic animal (human or experimental animal) is sufficiently suppressed to reach the target value. Since the control coefficient of the cooling temperature T is set and controlled from each reference value of the constant and the dead time, the intracranial pressure can be adjusted accurately and quickly to a desired pressure range, and at the same time, the brain temperature is always kept in a safe temperature range. be able to.

The gain of intracranial pressure due to temperature change, from the reference value of the time constant and dead time, the proportional coefficient of the cooling temperature T due to the difference e between the measured value and the target value of the intracranial pressure P K _P, the integral coefficient K _I and the differential determined coefficient K _D, since the cooling temperature T for PID feedback control using these control coefficient, suppresses sufficiently small overshoot of intracranial pressure and brain temperature, intracranial pressure can be adjusted exactly to the desired pressure range at an early stage .

Further, based on the difference e between the target value and the measured value of the intracranial pressure P, proportional coefficient K _P of the cooling temperature T determined from the reference _value, is corrected integral coefficient K _I and the differential coefficient K _D, initialization Even if the value does not match the target thermostat, it can be learned and optimized from the actually measured intracranial pressure, and the intracranial pressure can be brought to the desired pressure range at an early stage without overshooting. Can be adjusted.

  In addition, a blood temperature sensor supplied to the brain is provided, and is supplied to the brain by controlling the cooling temperature T of the cooling device so that the measured blood temperature is equal to or higher than the lowest temperature within the safe range of brain temperature. Since the blood temperature is always lower than the brain temperature and the heat energy in the brain is washed out, the brain temperature can be controlled essentially stably above the minimum temperature within its safe range.

Moreover, the whole body of a constant temperature animal (for example, person) can be cooled effectively by comprising a cooling device with an enclosure, a refrigerant | coolant supply apparatus, and a medium cooler.
In addition, by configuring the cooling device with a cooling plate, a cooling Peltier element, a heating Peltier element, and a cooling control device, the body of the small animal can be easily cooled and heated even if the constant temperature animal is an experimental small animal. Temperature can be maintained.

  According to the apparatus and method of the present invention, the management of intracranial pressure by cerebral cryotherapy, which has been difficult even for skilled medical workers, can be safely performed even by a less experienced worker. This eliminates the need for continuous monitoring of intracranial pressure for a long time, greatly reducing the burden on healthcare professionals, and essentially preventing brain temperature from becoming a dangerous temperature that can cause cardiac dysfunction. It is possible to accurately adjust the body temperature of the animal, and to obtain effects such as that it is possible to easily verify the therapeutic effect of hyperthermia by intracerebral hypothermia therapy in experimental animals.

Therefore, comprehensively, it can contribute to the automation of the most difficult part of medical treatment, automating the measurement and control of intracranial pressure, automating intracranial pressure management and brain temperature management with high accuracy, and protecting the cranial nerves of brain cryotherapy Not only is it beneficial to action, it can also help reduce intracranial pressure in cerebral cryotherapy.
At the same time, the automation of this physiological state management reduces the labor of medical staff in clinical practice, leads to a reduction in the medical costs of brain hypothermia, and frees medical staff from complicated temperature adjustments. The practitioner can concentrate on other more specialized medical procedures.

  Hereinafter, preferred embodiments of the present invention will be described with reference to the drawings. In the present invention, the constant temperature animal as the subject means a human (for example, a head trauma patient with hypercranial hypertension) or an animal (small experimental animal).

  FIG. 1 is a diagram of a first embodiment of an apparatus according to the present invention. In this figure, the simultaneous control device for intracranial pressure and brain temperature of the present invention is for human brain low-temperature treatment. Intracranial pressure sensor 12, brain temperature sensor 14, blood temperature sensor 16, cooling device 20, and control device 30 Is provided.

The intracranial pressure sensor 12 and the brain temperature sensor 14 measure the intracranial pressure and the brain temperature of the thermostatic animal, respectively. The intracranial pressure sensor 12 and the brain temperature sensor 14 are a pressure sensor and a temperature sensor that are inserted into the brain membrane or subarachnoid space of the thermostat 1 and directly detect the hydrostatic pressure and temperature of the cerebrospinal fluid of the thermostat 1. preferable. By using such a pressure sensor and a temperature sensor, the intracranial pressure and the brain temperature can be detected with high accuracy.
The intracranial pressure sensor 12 and the brain temperature sensor 14 are not limited to sensors that directly detect the hydrostatic pressure and temperature of cerebrospinal fluid, but may be other types of sensors.
These pressure sensors and temperature sensors output the detected pressure and temperature as electrical signals, and the electrical signals are input to the control device 30.

The blood temperature sensor 16 is preferably a temperature sensor that detects the blood temperature supplied to the brain of the thermostatic animal 1. By using such a temperature sensor, it is possible to detect the blood temperature supplied to the blood vessels of the brain with high accuracy.
The blood temperature sensor 16 may be a body temperature sensor that measures the body temperature of the constant temperature animal 1. The blood (cerebral blood flow) supplied to the brain has a function of washing out local heat energy of the brain, and the temperature is always lower than the brain temperature. The body temperature is almost the same as or slightly lower than the blood temperature. Therefore, in the control described later, even if the body temperature is used instead of the blood temperature, it is a safe side for control.

The cooling device 20 cools the body of the constant temperature animal 1 at a predetermined cooling temperature T. In the example of FIG. 1, the cooling device 20 includes an enclosure 21, a refrigerant supply device 22, and a medium cooler 23.
The surrounding body 21 is configured in a sleeping bag shape or a futon shape so as to surround at least a large part of the trunk of the thermostatic animal 1. A flexible tube through which a cooling medium (water or air) passes is incorporated inside the enclosure 21, and the cooling medium is supplied into the enclosure 21 by the refrigerant supply device 22. The cooling medium that has passed through the inside of the enclosure 21 and has risen in temperature is preferably returned to the refrigerant supply device 22 and recirculated.
The medium cooler 23 includes a cooling unit that cools the cooling medium (water or air) and a temperature controller that controls the temperature of the cooling medium, and cools and holds the temperature of the cooling medium to a predetermined cooling temperature T. The predetermined cooling temperature T is preferably about 5 to 6 ° C., for example, 27 to 31 ° C. lower than the safe temperature range (for example, 33 to 36 ° C.) of the thermostat 1.

The control device 30 is a PC (computer) provided with an input device 31, a storage device 32, an arithmetic device 33, and an input / output device (A / D converter 34, D / A converter 35), and the measured skull The cooling temperature T of the cooling device 20 is controlled based on the internal pressure and the brain temperature.
The input device 31 is, for example, a keyboard, and includes a safe range of the intracranial pressure and brain temperature of the thermostat 1, gains of the intracranial pressure due to changes in body temperature of the thermostat 1, reference values of time constant and dead time, and a target of the intracranial pressure. A value is input, and each of these data is stored in the storage device 32.
The data of these safety ranges and each reference value is obtained in advance by simulation or the like according to the type of the thermostat 1 (human, mouse, other small animal for experiment) and its characteristics (gender, age, weight, etc.). Is good.
For example, when the thermostat 1 is a human, the normal range of intracranial pressure is about 5 to 15 mmHg, and the safe range is about 20 mmHg or less. Moreover, the normal range of brain temperature is about 36-37 degreeC, and a safe range is about 33 degreeC or more. Further, the gain, time constant, and dead time of the intracranial pressure can be obtained by a simulation targeting the thermostatic animal 1 as shown in an example described later. Further, the target value of the intracranial pressure is appropriately set by a medical worker or the like within the safe range.

The control device 30 calculates the difference e between the target value and the measured value of the intracranial pressure P from the reference values of the gain of the intracranial pressure, the time constant and the dead time stored in the storage device 32 by the arithmetic unit 33. A proportional coefficient K _P , an integral coefficient K _I and a differential coefficient K _D of the cooling temperature T are obtained.
Furthermore, the control device 30 uses these to perform PID feedback control of the cooling temperature T so as to reach the target value of the intracranial pressure while suppressing the overshoot of the intracranial pressure and the brain temperature. The amount of overshoot of intracranial pressure is preferably about 2 mmHg or less, and the amount of overshoot of brain temperature is preferably 0.5 ° C. or less.

Further, the control device 30 has a correction calculation function, and the cooling temperature obtained from each reference value so that the difference e between the target value and the measured value of the intracranial pressure P measured during the PID feedback control approaches 0. T proportionality factor _{K P,} to correct the integral coefficient _{K I} and the differential coefficient _{K D.}

  Furthermore, the control device 30 controls the cooling temperature T of the cooling device so that the blood temperature measured by the blood temperature sensor 16 described above is equal to or higher than the lowest temperature within the safe range of brain temperature.

FIG. 2 is a relationship diagram between brain temperature and elapsed time in human brain hypothermia therapy. In this figure, the horizontal axis represents elapsed time (hours: h, days: d, weeks: w), and the vertical axis represents brain temperature (° C.).
When the brain temperature reaches 35 ° C., a biological defense reaction such as heat generation in the body due to shivering against hypothermic invasion occurs, and when the brain temperature becomes 33 ° C. or less, cardiac function decreases and arrhythmia occurs. In addition, if the cooling rate is too fast, there may be a dangerous temperature (32 ° C. or lower) that may cause cardiac dysfunction.
Therefore, it is preferable to slowly lower the brain temperature to 33-34 ° C. after a period of habituation of the living body is provided when the brain temperature reaches 35 ° C. and maintained at 35 ° C. for a while. In order to suppress the appearance of shivering, a muscle relaxant, panchronium bromide may be administered.
In addition, the period during which the brain temperature is maintained at 33 to 34 ° C. is within 6 days in consideration of the course of acute brain pathogenesis (about 6 days) and the onset of functional deterioration of the immune prevention mechanism (2 to 4 days). It is good to do.
Thereafter, after the intracranial pressure is stabilized within the normal range and the trend electroencephalogram is improved from the δ wave to the θ wave, rewarming is started.

In the present invention, the “safe range of brain temperature” includes the above-described temperature range, cooling rate, and rewarming rate. That is, when the constant temperature animal 1 is a human, the normal range of the brain temperature is about 36 to 37 ° C., and the safe range is about 33 ° C. or more, but when the brain temperature reaches 35 ° C., it is 2 to 3 hours. And then lowering the brain temperature to 33-34 ° C. at a cooling rate of less than about 0.5 ° C./h.
In addition, the period during which the brain temperature is maintained at 33 to 34 ° C. is 6 days or less at the maximum, and at the time of recovery, at least 34 days or 35 ° C., with a break-in period of 1 to 3 days. It is recommended that the temperature be slowly restored to a normal temperature of about 36 ° C. over a period of days.

  In the present invention, the intracranial pressure and the brain temperature are constantly measured, and the cooling temperature T of the cooling device is controlled so that the brain temperature is within the above-described safe range and the intracranial pressure reaches the target value.

  FIG. 3 shows a second embodiment of the device according to the invention. In this figure, the device of the present invention is for a small animal experiment, and includes an intracranial pressure sensor 12, a brain temperature sensor 14, a blood temperature sensor 16, a cooling device 20, and a control device 30.

In this example, the cooling device 20 includes a cooling plate 24, a cooling Peltier element 25, a heating Peltier element 26, and a cooling control device 27.
The cooling plate 24 is a metal plate having high thermal conductivity on which the body of the thermostatic animal 1 (in this example, an experimental animal) is placed.

The cooling Peltier element 25 contacts a part of the lower surface of the cooling plate 24 to cool the cooling plate. The heating Peltier element 26 contacts a part of the lower surface of the cooling plate 24 and heats the cooling plate.
The cooling Peltier element 25 and the heating Peltier element 26 use the Peltier effect in which heat is generated or absorbed when a current flows through a joint surface of different metals. By flowing a current through the cooling Peltier element 25 The cooling plate 24 is cooled, and the cooling plate 24 is heated by passing a current through the heating Peltier element 26.
Each of the Peltier elements 25 and 26 may be one or plural. In a plurality of cases, each of the cooling plates 24 is dispersed and pasted on the lower surface of the cooling plate 24 so that the entire surface of the cooling plate 24 can be cooled or heated to a uniform temperature.

  In this example, the cooling control device 27 has a switching circuit, and switches the power source from the DC power source 28 to either the Peltier element 25 or 26 in accordance with a command from the control device 30, and controls cooling or heating to cool the cooling device. The temperature of the plate 24 is cooled and held at a predetermined cooling temperature T.

Furthermore, in this example, it has the heat insulation case 41 which accommodates the thermostat 1 inside, and can supply the anesthetic and respiratory gas for laboratory animals in the heat insulation case 41 here. In this example, a micro pump 42 for supplying medicine to be administered to the thermostat 1 is provided, and the supply amount is controlled by the control device 30.
Other configurations are the same as those in FIG.

  FIG. 4 is a flowchart of a method for simultaneously controlling intracranial pressure and brain temperature according to the present invention. The method of the present invention includes an intracranial pressure sensor 12 and a brain temperature sensor 14 that respectively measure the intracranial pressure and brain temperature of the thermostat 1 and a cooling device 20 that cools the body of the thermostat at a predetermined cooling temperature T. As shown in the figure, the apparatus control method includes an input step S1, a storage step S2, a setting step S3, a control step S4, and a correction step S5.

In the input step S1, the safe range of the intracranial pressure and brain temperature of the constant temperature animal 1, the gain of the intracranial pressure due to the change in body temperature of the constant temperature animal 1, the reference values of the time constant and dead time, and the target value of the intracranial pressure are stored on the PC (computer). ).
In the storing step S2, the inputted safety range, gain, time constant, dead time reference value and intracranial pressure target value are stored.
In the setting step S3, the proportionality of the cooling temperature T based on the difference e between the target value and the measured value of the intracranial pressure P is determined from each reference value so that the overshoot of the intracranial pressure and the brain temperature are sufficiently reduced to reach the target value. coefficients _{K P,} to set the integral coefficient _{K I} and the differential coefficient _{K D.}

In the control step S4, the cooling temperature T is fed back to the PID using the set proportional coefficient K _P , integral coefficient K _I and differential coefficient K _D based on the intracranial pressure and brain temperature measured by the intracranial pressure sensor and the brain temperature sensor. Control,
In this control step, the cooling temperature T of the cooling device is controlled so that the blood temperature measured by the blood temperature sensor 16 is equal to or higher than the lowest temperature in the safe range of brain temperature.

In the correction step S4, based on the difference e between the measured value and the target value of the intracranial pressure P, and corrects the proportional coefficient K _P, the integral coefficient K _I and the differential coefficient K _D of the cooling temperature T determined from the reference value

  According to the apparatus and method of the present invention described above, the gain of the intracranial pressure due to body temperature change so as to reach the target value while suppressing the overshoot of the intracranial pressure and brain temperature of the thermostat 1 (human or animal), Since the control coefficient of the cooling temperature T is set and controlled from each reference value of time constant and dead time, the intracranial pressure can be adjusted accurately and quickly to the desired pressure range, and at the same time the brain temperature is always kept in a safe temperature range. can do.

The gain of intracranial pressure due to temperature change, from the reference value of the time constant and dead time, the proportional coefficient of the cooling temperature T due to the difference e between the measured value and the target value of the intracranial pressure P K _P, the integral coefficient K _I and the differential determined coefficient K _D, since the cooling temperature T for PID feedback control using these control coefficient, suppresses sufficiently small overshoot of intracranial pressure and brain temperature, intracranial pressure can be adjusted exactly to the desired pressure range at an early stage .

Further, based on the difference e between the target value and the measured value of the intracranial pressure P, proportional coefficient K _P of the cooling temperature T determined from the reference _value, is corrected integral coefficient K _I and the differential coefficient K _D, initialization Even if the value does not match the target thermostat, it can be learned and optimized from the actually measured intracranial pressure, and the intracranial pressure can be quickly adjusted to the desired pressure range while suppressing overshoot. .

In addition, a blood temperature sensor supplied to the brain is provided, and is supplied to the brain by controlling the cooling temperature T of the cooling device so that the measured blood temperature is equal to or higher than the lowest temperature within the safe range of brain temperature. Since the blood temperature is always lower than the brain temperature and the heat energy in the brain is washed out, the brain temperature can be controlled essentially stably above the minimum temperature within its safe range.

Examples of the present invention will be described below.

[Assumptions]
In order to model the circulating thermal system of a human (patient living body), the following hypothetical conditions were set based on clinical practice of cerebral cryotherapy.
(1) Since patients with cerebral cryotherapy are placed under general anesthesia, the neural and humoral regulatory functions in the body are ignored, and the patient's circulatory and thermal system is made a completely passive system.
(2) Corresponding to the anatomical physiology, as shown in FIG. 5, the patient's living body is converted into a skull 1a (cerebrospinal fluid, brain parenchyma, cerebral blood vessel), cardiovascular 1b (arterial part, vein), lung 1c (parenchymal, Approximation with 6 segments (13 compartments) of blood vessel), viscera 1d (parenchyma, blood vessel), muscle 1e (parenchyma, blood vessel), and other 1f (parenchyma, blood vessel), and created a circulation thermal system model shown in FIG. .

(3) The hydrostatic pressure and temperature of cerebrospinal fluid are representative of intracranial pressure and brain temperature. The reason is that these physiological state quantities can be accurately measured by a sensor placed in the ventricle or subarachnoid space.
(4) Assume that the environmental temperature of the muscle segment can be changed and the other segments are insulated in response to the clinical cooling action. There is no heat balance due to artificial replacement fluid and urine excretion in the visceral segment. Ignore heat and water losses from the respiratory system.
(5) The flow of water and heat between segments depends on blood flow and lymph flow. There is water filtration and heat conduction between the parenchyma and vascular compartments in the segment. Metabolic water production and heat production occur only in parenchyma. The osmotic pressure in each compartment is constant.
(6) Corresponding to the heartbeat output, pressure pumps are introduced into the arterial and venous portions of the cardiovascular segment to give a constant pressure increase to the systemic and pulmonary circulation, respectively. Therefore, the hydrostatic pressure of each compartment can be set in a physiologically normal range.
Under these assumptions, a circulating thermal system model of the patient's living body is constructed with the cooling temperature as input and the intracranial pressure as output.

[Circulating thermal system model]
According to the conservation law of matter and energy, differential equations for hydrostatic pressure and temperature in each compartment can be created. Such differential equations are omitted here.
Cerebrospinal fluid secretion, metabolic water production and heat production, and water filtration coefficient between compartments take temperature dependence into consideration.

[Parameter settings]
The physiological and physical parameters of the circulating thermal model are basically based on literature, and estimated values and assumed values are also used as necessary. The temperature and pressure dependence is nonlinear, and the circulation thermal model of the patient's living body is also nonlinear. Therefore, the theoretical solution may be, for example, the Runge-Kutta numerical analysis method.

[Model validation]
[Characteristics of brain temperature change for step cooling]
FIG. 7 is a brain temperature response diagram of a circulating thermal model with respect to a step-like cooling input. In this figure, the horizontal axis represents elapsed time, and the vertical axis represents brain temperature.
As can be seen from this figure, with respect to the change in the cooling temperature (from 30 ° C. to 29 ° C.), the brain temperature hardly changes at first and changes suddenly after a while. After that, it changes slowly and finally becomes a constant value. That is, the brain temperature change has the characteristics of dead time and first order lag.
From this figure, as a step response characteristic of brain temperature, it is estimated that the time constant is 9.2 h, the dead time is 0.6 h, and the gain is 2.0 ° C./° C.

In clinical practice of brain hypothermia, it has been reported that it takes 3 to 11 h to cool a patient's brain temperature to a target low temperature. Although there is no strict definition such as step response and time constant in the clinic, in the concept of “several hours”, the brain temperature change of the circulating thermal model is consistent with the cooling characteristics of clinical patient brain temperature.
Moreover, it has been reported that there is a dead time of 0.5 to 0.75 h in the living body deep temperature change with respect to the environmental temperature change, which is consistent with the estimated dead time of 0.6 h according to this figure. If metabolic heat production is reduced due to a decrease in body temperature and there is no body temperature regulation mechanism, a further decrease in body temperature may occur. It is clear that the estimated gain of 2.0 ° C / ° C is consistent with this physiological fact.
From these, it can be said that the thermal system part of the circulation thermal model is appropriate.

[Characteristics of intracranial pressure change with increasing impulse volume]
An infusion test is performed in the clinic as a test method for cerebrospinal fluid circulatory disturbance. This test method is equivalent to injecting a certain volume of water into the cerebrospinal fluid of a circulating thermal model in a short time.
FIG. 8 is a response characteristic diagram of intracranial pressure to an increase in cerebrospinal fluid. In this figure, the horizontal axis represents elapsed time, and the vertical axis represents changes in intracranial pressure. In this simulation, 2 ml of water was given to the cerebrospinal fluid compartment at a rate of 0.66 ml / s in 10-12 seconds.
As can be seen from this figure, the intracranial pressure rises during the water injection, and a maximum pressure change of about 3.6 mmHg occurs at the end of the injection. Thereafter, the intracranial pressure returns to the pressure state before the injection.
These results are in good agreement with previously reported research results, and it can be said that the circulatory system part of the circulating thermal model is also valid.

[Apply model]
[Modeling of intracranial hypertension]
Intracranial hypertension seen in postoperative head trauma patients may be due to angiogenic cerebral edema.
Here we simulate angiogenic brain edema. For this purpose, the water filtration coefficient of the blood brain barrier and blood cerebrospinal fluid barrier in the skull segment is set to 1000 times the normal value, whereby the intracranial pressure of the circulating thermal model becomes 20 mmHg.
The present invention uses this as a patient model for intracranial hypertension.

[Response characteristics of intracranial hypertension to stepped cooling]
FIG. 9 is a response characteristic diagram of the intracranial pressure by stepped cooling input. In this figure, the horizontal axis represents elapsed time and the vertical axis represents intracranial pressure.
As can be seen from this figure, the step response of the intracranial pressure with respect to the cooling temperature has characteristics of dead time and first-order lag, similar to the step response of brain temperature. If the non-linearity of the intracranial pressure response is ignored in consideration of clinical practicality, the gain is 5.0 mmHg / ° C, the time constant is 9.9 h, and the dead time is 1.0 h from the intracranial pressure drop curve in this figure. Can be approximated.
In other words, the action of lowering intracranial pressure due to cooling can be quantified by these data, and clinical application can be expected as a quantitative index for adjusting the cooling temperature for intracranial pressure management.

[Fixed value control of intracranial hypertension]
Using the characteristic approximation data described above, the feasibility of automatic control of intracranial hypertension by PID feedback control is shown.
Specifically, the above-mentioned patient model of intracranial hypertension is used as a substitute for an actual patient's living body, and the intracranial pressure is made to follow a preset intracranial pressure management target value. For this purpose, the cooling temperature setting is given by equation (1).

Here, e is the difference between the target value of the intracranial pressure and the estimated value based on the circulating thermal model. K _P , K _I , and K _D are parameters for PID feedback control, respectively.
In the simulation, the intracranial pressure value 9.9 mmHg in the normal range is set as a target value, and K _P = 1.2 ° C./mmHg, K _I = 1.2 h, K _D = 0. Set to 5 h.

FIG. 10 is a diagram showing simulation results of intracranial pressure and brain temperature according to the present invention. In this figure, the horizontal axis represents elapsed time, and the vertical axis represents brain temperature, cooling temperature, and intracranial pressure.
As can be seen from this figure, by the cooling input (cooling temperature change) given by the present invention, the intracranial pressure was decreased from the enhanced state to the target value, and stable control could be performed. During this time, the brain temperature is also maintained within a safe range.
Specifically, the intracranial pressure was lowered to the target value within 4 h after cooling, and a maximum intracranial pressure drop rate of 4.2 mmHg / h was obtained at 1.7 h. At 6 h after cooling, after a very small overshoot (about 1.2 mmHg), the intracranial pressure was within the target value (within 0.2% error).

In addition, the brain temperature decreased on a time scale similar to the drop in intracranial pressure, and was finally maintained at about 33 ° C. This suggests that brain temperature management and intracranial pressure management in brain cryotherapy are consistent. It was shown that the cooling temperature for lowering the intracranial pressure was initially set low, then increased, and finally maintained at 28 ° C. or lower. Such temperature adjustment is almost consistent with the temperature management of cerebral cryotherapy currently practiced clinically.
At the same time, it became clear from the linear characteristic approximation data that PID feedback control applicable to clinical practice can be applied, and that automatic control of intracranial pressure by automatic adjustment of the cooling temperature can be realized.

  It should be noted that the present invention is not limited to the above-described embodiment, and can be variously modified without departing from the gist of the present invention.

1 is a diagram of a first embodiment of an apparatus according to the present invention. It is a related figure of the brain temperature and elapsed time in a human brain cryotherapy. FIG. 3 is a diagram of a second embodiment of the device according to the invention. It is a flowchart of the simultaneous control method of the intracranial pressure and brain temperature by this invention. It is explanatory drawing of a human circulation thermal system. It is a model figure of a human circulation thermal system. It is a brain temperature response figure of the circulation thermal model with respect to cooling input. It is a response characteristic figure of the intracranial pressure with respect to the increase in cerebrospinal fluid. It is a response characteristic figure of the intracranial pressure by cooling input. It is a figure which shows the simulation result of the intracranial pressure and brain temperature by this invention. 1 is a schematic diagram of “Intracranial Pressure Detection Device” of Patent Document 1. FIG. 6 is a schematic diagram of “Intracranial Pressure Gauge” of Patent Document 2. FIG. It is a schematic diagram of the apparatus of patent document 3. FIG. FIG. 6 is a schematic view of “Body temperature maintaining device for small animals” of Patent Document 4.

Explanation of symbols

1 constant temperature animal, 12 intracranial pressure sensor, 14 brain temperature sensor, 16 blood temperature sensor,
20 Cooling device, 21 Enclosure, 22 Refrigerant supply device, 23 Medium cooler,
24 cooling plate, 25 Peltier element for cooling, 26 Peltier element for heating,
27 Cooling control device, 28 DC power supply,
30 control device (computer), 31 input device, 32 storage device,
33 arithmetic unit, 34 A / D converter, 35 D / A converter,
41 Insulation case, 42 Micro pump

Claims (10)

An intracranial pressure sensor and a brain temperature sensor for measuring the intracranial pressure and brain temperature of the thermostat animal, respectively;
A cooling device for cooling the body of the constant temperature animal at a predetermined cooling temperature T;
A control device for controlling the cooling temperature T based on the measured intracranial pressure and brain temperature,
The control device includes a storage device for storing the reference values of the safe range of the intracranial pressure and brain temperature, the gain of the intracranial pressure due to body temperature change, the time constant, and the dead time,
The intracranial pressure and the brain are controlled by setting a control coefficient of the cooling temperature T from each of the reference values so that the overshoot of the intracranial pressure and the brain temperature is sufficiently reduced by the control device to reach the target value. Simultaneous temperature control device. The control coefficients are a proportional coefficient K _P , an integral coefficient K _I, and a differential coefficient K _D of the cooling temperature T due to a difference e between the target value and the measured value of the intracranial pressure P,
The control device according to claim 1, wherein the proportional coefficient K _P of the cooling temperature T determined from the reference _value, the PID feedback control of the cooling temperature T using the integral coefficient K _I and the differential coefficient K _D, characterized in that The simultaneous control device of intracranial pressure and brain temperature described in 1. The control device corrects the proportional coefficient K _P , the integral coefficient K _I, and the differential coefficient K _D of the cooling temperature T obtained from each reference value based on the difference e between the target value and the measured value of the intracranial pressure P. The simultaneous control device for intracranial pressure and brain temperature according to claim 2, which has a calculation function. Equipped with a blood temperature sensor that measures the blood temperature supplied to the brain of the thermostat animal,
2. The intracranial pressure and brain temperature according to claim 1, wherein the control device controls the cooling temperature T of the cooling device so that the measured blood temperature is equal to or higher than a minimum temperature within a safe range of brain temperature. Simultaneous control device.   The cooling device includes an enclosure that surrounds the body of a constant temperature animal, a refrigerant supply device that supplies a cooling medium into the enclosure, and a medium cooler that cools and holds the temperature of the cooling medium to a predetermined cooling temperature T. The simultaneous control device for intracranial pressure and brain temperature according to claim 1, wherein:   The cooling device includes a cooling plate on which the body of a constant temperature animal is placed, a Peltier element for cooling that cools the cooling plate by contacting a part of the lower surface of the cooling plate, and a cooling plate that contacts the part of the lower surface of the cooling plate. A heating Peltier element for heating, and a cooling control device for passing a current through the cooling Peltier element or the heating Peltier element and cooling and holding the temperature of the cooling plate at a predetermined cooling temperature T. Item 2. The intracranial pressure and brain temperature simultaneous control device according to item 1. A method for controlling an apparatus comprising an intracranial pressure sensor and a brain temperature sensor for measuring an intracranial pressure and a brain temperature of a thermostat animal, respectively, and a cooling device for cooling the body of the thermostat animal at a predetermined cooling temperature T,
A storage step for storing each of the reference values of the safe range of the intracranial pressure and brain temperature, the gain of the intracranial pressure due to a change in body temperature, the time constant, and the dead time;
A setting step for setting a control coefficient of the cooling temperature T from each of the reference values so as to reach the target value while suppressing the overshoot of the intracranial pressure and the brain temperature sufficiently;
A control step of controlling the cooling temperature T by using the set control coefficient based on the intracranial pressure and the brain temperature measured by the intracranial pressure sensor and the brain temperature sensor. Simultaneous temperature control method. In the setting step, from each of the reference values, a proportional coefficient K _P , an integral coefficient K _I and a differential coefficient K _D of the cooling temperature T according to the difference e between the target value and the measured value of the intracranial pressure P are set,
In the control step, the proportional coefficient K _{P set,} integration coefficient K using the _I and differential coefficient K _D for PID feedback control of the cooling temperature T, the possible intracranial pressure and cerebral temperature according to claim 7, wherein Simultaneous control method. Based on the difference e between the target value and the measured value of the intracranial pressure P, having a correction step of correcting the proportional coefficient K _P, the integral coefficient K _I and the differential coefficient K _D of the cooling temperature T determined from the reference value, it The method for simultaneously controlling intracranial pressure and brain temperature according to claim 8. Equipped with a blood temperature sensor that measures the blood temperature supplied to the brain of the thermostat animal,
The intracranial pressure and brain temperature according to claim 7, wherein, in the control step, the cooling temperature T of the cooling device is controlled so that the measured blood temperature is equal to or higher than a minimum temperature within a safe range of brain temperature. Simultaneous control method.

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