JP5224995B2 - Analgesic evaluation method, analgesic management method, and analgesic management device in endoscopic submucosal dissection under conscious sedation - Google Patents

Description

  The present invention relates to a patient pain detection method, analgesic degree evaluation method, and analgesic management method in an endoscopic submucosal dissection (hereinafter sometimes abbreviated as ESD) under conscious sedation. About. Specifically, the present invention relates to conscious sedation endoscopy, characterized by measuring amylase of a saliva sample collected from a patient or its activity and detecting an increase in salivary amylase or its activity. The present invention relates to a pain detection method, an analgesic degree evaluation method, and an analgesic management method for a patient in mirror submucosal dissection.

  The present invention also relates to an analgesic management device used in a sedation method, specifically a drug supply device and a notification device.

  In surgery and the like, anesthesia is generally performed to reduce patient pain. This anesthesia includes local anesthesia and general anesthesia, but general anesthesia is often adopted in open surgery. In general anesthesia, a so-called anesthetic is administered. General anesthesia has advantages such as unconsciousness of the patient, strict whole-body management, and sufficient operating time. On the other hand, general anesthesia has drawbacks such as the need for an anesthesiologist, large preparation, and high cost.

  An alternative to the general anesthesia described above is sedation. In sedation, patients are given sedation and analgesics. The sedation method produces an amnestic effect on the patient and can reduce pain in a relatively lightly invasive surgical operation using an endoscope. The sedation is advantageous in that it does not require an anesthesiologist, is easy to prepare and does not necessarily require an operating room, and is relatively inexpensive. On the other hand, the sedation method has drawbacks such as that the whole body management is not strictly performed, the patient's consciousness may be restored, and the operation time is not sufficient. Such sedation methods are used in intensive care and dental treatment as well as surgery, although there are differences in sedation levels.

  For example, endoscopic submucosal dissection for early gastric cancer has been performed in many facilities in recent years, but in general, deep sedation is selected over general anesthesia. . However, it is often seen that the operation time required for ESD becomes longer as the indication expands, and an appropriate intraoperative management index is required.

  In endoscopic treatment without a surgical body surface wound, one of the invasion to a living body is considered to be stress, and stress is expected to be high in long-term treatment. Until now, however, objective evaluation has been difficult.

  By the way, amylase exists in human blood and saliva, and this amylase is measured by blood tests and the like. As a method for measuring amylase in saliva, an enzyme method, an electrode method, and the like are known (Patent Documents 1 to 3). Further, a method for determining stress using α-amylase activity in saliva as an index has been proposed (Patent Document 4).

  In recent years, it has been reported (Non-Patent Document 1) that stress can be evaluated quickly and non-invasively by amylase activity in saliva, and has been put into practical use. Under stress, the hypothalamus induces excitement of the sympathetic nervous system, and as a result, norepinephrine is secreted by direct neural action by the sympathetic nervous system, amylase is synthesized in the salivary glands, and amylase is secreted in saliva. In addition, stress-induced sympathetic nervous system excitement causes norepinephrine secretion in the adrenal medulla and increases blood norepinephrine concentration, resulting in amylase synthesis and salivary amylase secretion in the salivary glands. The increase in salivary amylase is detected in about 1 to several minutes after the excitement of the sympathetic nervous system. Thus, the salivary amylase activity is considered as an index for evaluating the nerve activity of the sympathetic / adrenal medullary system (SAM system).

  In addition, there is a relationship between salivary amylase activity and the pain level of patients with chronic pain, and it has been reported that salivary amylase activity can be used for evaluation of pain level (Non-patent Document 2).

  However, there is no report of an index that can objectively evaluate pain during surgery in patients under sedation, and there is no report that salivary amylase activity can be used as such an index.

JP 2004-267202 A JP 2004-24236 A JP 2004-121214 A JP 2002-168860 A Masaki Yamaguchi, “Nichi Pharmacology”, 2005, Vol. 129, p. 80-84. Shirasaki, S. et al., “Correlation between salivary alpha-amylase activity and pain scale in es 2 in the es and in the pain with the pain in the med. p. 120-123.

  It is an object of the present invention to provide an objective index for assessing patient pain in sedation to detect patient pain during surgery and treatment in order to safely perform surgery and treatment of the patient in sedation It is to provide a method for evaluating the degree of analgesia of an analgesic administered for surgery and treatment, and a method for managing analgesia of a patient during surgery and treatment.

  In the sedation method described above, the present inventors have confirmed that the patient does not feel pain at all. Specifically, when a questionnaire was given to patients who underwent endoscopic submucosal dissection, all patients who received general anesthesia answered that they did not remember anything during the operation. On the other hand, about 40% of the patients who were treated with sedation answered that it was somewhat difficult.

  The present invention has been made under such a background, and in addition, an object of the present invention is to provide a means for determining that a patient in sedation feels pain and administering a sedative or analgesic. And

  The present inventors have intensively studied to achieve the above object, and in ESD under conscious sedation for patients with early gastric cancer, amylase activity in the patient's saliva sample increases during ESD, and It has been found that the increased amylase activity decreases with the administration of analgesics. Based on this, the present inventors have found that an increase in salivary amylase or its activity is an objective indicator of patient pain in ESD under conscious sedation, and using this objective indicator, A method for detecting pain in a patient undergoing ESD under sedation, evaluating the level of analgesia with an intraoperative analgesic agent, and managing intraoperative analgesia, and an analgesic management apparatus were established. The present invention has been achieved based on these findings.

  That is, the present invention relates to endoscopic submucosal dissection under conscious sedation, characterized by measuring amylase in saliva samples collected intermittently or continuously and detecting an increase in salivary amylase The present invention relates to a method for detecting pain.

  The present invention also relates to the pain detection method, wherein the saliva sample is a saliva sample collected intermittently.

  Furthermore, the present invention provides the detection of any one of the above pains, wherein amylase in a saliva sample is measured and an increase in salivary amylase is detected, the amylase activity in the saliva sample is measured and an increase in salivary amylase activity is detected. Regarding the method.

  Furthermore, the present invention relates to the method for detecting pain, wherein the increase in salivary amylase activity is an increase of 20 kU / L or more compared to the salivary amylase activity before treatment.

  The present invention also relates to any one of the methods for detecting pain, wherein the conscious sedation is introduced by intravenous administration of midazolam and pentazocine.

  Furthermore, the present invention relates to any one of the pain detection methods described above, wherein the endoscopic submucosal dissection is an endoscopic submucosal dissection for gastric cancer.

  Furthermore, the present invention is characterized in that amylase activity of saliva samples collected intermittently is measured, and an increase in salivary amylase activity of 20 kU / L or more is detected as compared with saliva amylase activity before treatment. The present invention relates to a method for detecting pain in endoscopic submucosal dissection of conscious sedation introduced by intravenous administration of midazolam and pentazocine.

  The present invention also measures amylase activity in saliva samples collected intermittently or continuously, and when an increase in salivary amylase activity is detected, it is administered in endoscopic submucosal dissection under conscious sedation. The present invention relates to a method for evaluating the analgesic level of an analgesic in endoscopic submucosal dissection under conscious sedation, wherein the analgesic level of the applied analgesic is determined to have decreased.

  Furthermore, the present invention relates to a method for evaluating the analgesic level of the analgesic, which measures amylase activity of saliva samples collected intermittently.

  Furthermore, the present invention provides any one of the above analgesics, wherein the amylase in the saliva sample is measured and the increase in the salivary amylase is detected, the amylase activity in the saliva sample is measured and the increase in the salivary amylase activity is detected. It is related with the analgesic degree evaluation method.

  Moreover, this invention relates to the analgesic-degree evaluation method of the said analgesic whose increase in salivary amylase activity is an increase of 20 kU / L or more compared with the salivary amylase activity before a treatment.

  Furthermore, the present invention relates to a method for evaluating the analgesic level of any one of the above analgesics, wherein the conscious sedation is introduced by intravenous administration of midazolam and pentazocine.

  Furthermore, the present invention relates to a method for evaluating the analgesic level of any one of the above analgesic agents, wherein the endoscopic submucosal dissection is an endoscopic submucosal dissection for gastric cancer.

  In the conscious sedation method, the present invention measures amylase activity of saliva samples collected intermittently or continuously, and the administration of an analgesic is determined by detecting an increase in salivary amylase activity. The present invention relates to an analgesic management method in endoscopic submucosal dissection.

  Furthermore, this invention relates to the said analgesic management method which measures the amylase activity of the saliva sample extract | collected intermittently.

  Furthermore, the present invention provides the analgesia according to any one of the above, wherein measuring amylase in the saliva sample and detecting an increase in salivary amylase is measuring the amylase activity in the saliva sample and detecting an increase in salivary amylase activity. It relates to the management method.

  The present invention also relates to the analgesic management method, wherein the increase in salivary amylase activity is an increase of 20 kU / L or more compared to the salivary amylase activity before the treatment.

  Furthermore, the present invention relates to any one of the above analgesic management methods, wherein the conscious sedation method is introduced by intravenous administration of midazolam and pentazocine.

  Furthermore, the present invention relates to any one of the above analgesic management methods, wherein the endoscopic submucosal dissection is an endoscopic submucosal dissection for gastric cancer.

  Further, the present invention is based on saliva amylase activity measuring means for measuring amylase activity using saliva collected from a human subject to sedation as a specimen, and outputting measurement information indicating the measured value, based on the measurement information. Drug supply determining means for outputting supply information indicating supply of the drug, and holding at least one of a sedative or an analgesic as a drug to be supplied, and administering the drug held based on the supply information to the human The present invention relates to a medicine supply device comprising a medicine supply means for supplying as much as possible.

  In the present invention, the medicine supply determining means has a first threshold for determining whether or not to supply the medicine, and supplies the medicine based on a comparison between the measurement information and the first threshold. The present invention relates to the medicine supply device that outputs supply information to be supplied.

  Furthermore, the present invention relates to any one of the above-described drug supply devices, wherein the drug supply determining means determines the amount of the drug to be supplied based on the measured value, and outputs supply information including the drug amount to be supplied.

  Further, the present invention is based on saliva amylase activity measuring means for measuring amylase activity using saliva collected from a human subject to sedation as a specimen, and outputting measurement information indicating the measured value, based on the measurement information. The present invention relates to a notification device including notification determination means for outputting notification information indicating that notification is to be performed, and notification means for performing notification based on the notification information.

  Further, according to the present invention, the notification determining unit has a second threshold for determining whether or not to perform the notification, and outputs the notification information based on a comparison between the measurement information and the second threshold. The present invention relates to the notification device.

  According to the present invention, the salivary amylase or its activity in a collected saliva sample is measured, and an increase in salivary amylase or its activity is detected. It is possible to provide a method for detecting pain in an exfoliation method, a method for evaluating analgesia, and a method for managing analgesia.

  Since the method according to the present invention uses a saliva sample, there is less stress on the patient, and there is an advantage that it can be carried out quickly and easily because no complicated operation is required for collecting the saliva sample or measuring the salivary amylase activity. Yes, it is useful for intraoperative management in endoscopic submucosal dissection under conscious sedation.

  According to the present invention, an analgesic management device used in the sedation method, specifically, a medicine supply device and a notification device can be provided.

  According to the drug supply device of the present invention, the amylase activity in saliva collected from a human subjected to the sedation method is measured, it is determined whether or not the drug should be supplied based on the amylase activity, and the sedation method Therefore, when a sedated person feels pain, the drug is automatically administered and the amnestic effect is enhanced. Thereby, control of a sedation method is performed simply.

  Further, according to the notification device according to the present invention, amylase activity in saliva collected from a sedated person is measured, and it is determined whether notification should be performed based on this amylase activity. Therefore, based on this notification, a medical person administers a drug required for the sedation method to a human, and the amnesia effect is enhanced so as to remove the pain of the human subjected to the sedation method. Thereby, control of a sedation method is performed simply.

  Thus, the present invention shows an excellent effect in the pharmaceutical field.

  The present invention provides a method for detecting pain in a patient during surgery and treatment under sedation, characterized by measuring amylase in a collected saliva sample and detecting an increase in salivary amylase.

  As one aspect of the method according to the present invention, pain in endoscopic submucosal dissection under conscious sedation is characterized by measuring amylase in a collected saliva sample and detecting an increase in salivary amylase Can be provided.

  Saliva is collected intermittently or continuously. “Intermittently collected” means being collected at an appropriate interval. The collection interval is not particularly limited as long as the stress on the patient is low and the patient can feel early pain, and may be any interval as long as it is within 30 minutes. Can be applied at intervals of 30 minutes, more preferably 25 minutes, even more preferably 20 minutes, even more preferably 15 minutes, still more preferably 10 minutes, even more preferably 5 minutes, still more preferably 1 minute. Further, the collection interval is preferably constant, but can be changed as appropriate. “Continuously collected” means that the samples are collected without a gap.

  Saliva is collected in a short time without causing physical and mental stress on the patient. As a method for collecting saliva, any known collection method can be used as long as it can be collected in a short time without applying stress to the patient. For example, a method of collecting using a suction tool such as a dropper, and a method of collecting by suction using an instrument utilizing a capillary phenomenon such as a capillary can be exemplified.

  Salivary amylase can be measured by measuring the amount of salivary amylase using a known protein measurement method, or by measuring the enzyme activity of salivary amylase using a known measurement method. Since it can be measured in a short time, the measurement of salivary amylase is preferably carried out by measuring the enzyme activity of salivary amylase. Hereinafter, the enzyme activity of amylase may be simply referred to as amylase activity.

  As a method for measuring salivary amylase activity, any known method for measuring the enzyme activity of amylase can be used. Preferably, among the known methods, a method capable of measuring amylase activity in a short time is used. Specifically, for example, salivary amylase activity can be measured by using an amylase substrate, mixing saliva and the substrate, and detecting an enzyme reaction product produced by the reaction of the amylase and the substrate. Examples of amylase substrates include starch, oligosaccharides, and derivatives thereof. When α-2-chloro-4-nitrotophenyl-galactosyl maltoside (Gal-G2-CNP) is used as a substrate, the substrate is hydrolyzed by the presence of salivary amylase to produce Gal-G2 and CNP. The yellow color caused by the generated CNP can be colorimetrically determined, and the amylase activity can be measured by the change in absorbance of the color. In addition, when a synthetic oligosaccharide modified with a dye is used as a substrate, the substrate is hydrolyzed due to the presence of salivary amylase, and the dye is liberated to form a color. It can be measured. The measurement of salivary amylase activity can be carried out using such an apparatus because various apparatuses for measuring the enzyme activity of amylase are commercially available.

  The increase in salivary amylase can be detected by comparing salivary amylase in the saliva sample with a reference value. As a reference value, a measured value of amylase of a saliva sample before treatment, for example, a saliva sample before introduction into the conscious sedation method, a saliva sample immediately after introduction of the conscious sedation method, or a saliva sample immediately after the start of ESD can be used. Further, as a reference value, a measured value of amylase in a saliva sample collected last time of a saliva sample to be evaluated among a plurality of saliva samples collected and measured intermittently (hereinafter referred to as a previous measured value). Yes) can be used. Alternatively, a measurement value of amylase in a saliva sample collected immediately before the saliva sample to be evaluated among saliva samples continuously collected and measured can be used as a reference value. The increase in salivary amylase can be determined using the absolute value or rate of change of salivary amylase or its activity as an index. The rate of change refers to a reference value, in this case preferably the rate of increase compared to the previous measured value. The increase in salivary amylase can be determined by calculating an increase gradient between the previous measurement value and the next measurement value. When the increase in salivary amylase is determined by the increase in its activity, the increase is 20 kU / L or more, preferably 30 kU / L or more, more preferably 40 kU / L or more, and even more preferably 50 kU / L or more compared to the reference value. When recognized, it is determined that salivary amylase has increased. Alternatively, salivary amylase increased when an increase of 20% or more, preferably an increase of 30% or more, more preferably an increase of 40%, more preferably an increase of 50% or more was observed compared to the reference value. Is determined. When the increase in salivary amylase is determined by the increase in the amount, the increase in the amount of amylase used as a determination index correlates with the amount of amylase and the amylase activity. Can be obtained with reference to the increased value of the amylase activity.

  Examples of the sedative used in the conscious sedation include benzodiazepines such as midazolam and diazepam, and propofol. Preferably, midazolam is used. In general, sedatives are continuously microinjected to maintain sedation. The dose of the sedative may be a dose generally used in the conscious sedation method, and can be appropriately changed depending on the state of sedation induction of the patient. As the analgesic agent used in the sedative method under consciousness, pentazocine is preferable. In general, analgesics are administered together with sedatives at the time of introduction of sedation, and are administered as needed. The dose of the patient analgesic may be a dose generally used in conscious sedation, and can be appropriately changed depending on the analgesic state of the patient.

  Endoscopic submucosal dissection (ESD) is a surgical procedure using an endoscope used for excision of malignant tumors, preferably early malignant tumors. In ESD, first, the periphery of the cancer is sufficiently incised with an electric scalpel, and then the submucosal layer is peeled off from the muscular layer. Therefore, it is possible to excise without leaving a large lesion. Examples of malignant tumors to which ESD can be applied include gastrointestinal cancers such as gastric cancer, colorectal cancer, and esophageal cancer, preferably gastric cancer.

  The present invention also provides a method for evaluating the analgesic level of an analgesic agent in endoscopic submucosal dissection under conscious sedation, which comprises measuring amylase in a saliva sample. Here, “the analgesic level of the analgesic” means the degree of analgesic effect by the administered analgesic.

  In endoscopic submucosal dissection under conscious sedation, a sedative is introduced with a sedative and an analgesic is administered to reduce stress on the patient. The degree of the effect of this analgesic is evaluated using as an index the increase in amylase or its activity in the collected saliva sample.

  Detecting patient pain in endoscopic submucosal dissection with conscious sedation as described above by measuring amylase or its activity in saliva samples and detecting increased salivary amylase or its activity Can do.

  Therefore, it is possible to detect patient pain in endoscopic submucosal dissection under conscious sedation by measuring amylase or its activity in saliva samples and detecting an increase in salivary amylase or its activity. Thus, it can be determined that the analgesic level of the analgesic administered in the endoscopic submucosal dissection under conscious sedation has decreased.

  The present invention further provides an endoscopic conscious sedation method, characterized in that the amylase of a saliva sample or its activity is measured and the administration of an analgesic is determined by detecting an increase in salivary amylase or its activity. An analgesic management method in submucosal dissection is provided.

  In endoscopic submucosal dissection under conscious sedation, a sedative state is introduced with a sedative and an analgesic is administered to reduce pain in the patient. The analgesic is preferably administered as appropriate depending on the pain of the patient. For example, analgesics can be administered using body movement as an index of pain of the patient, but there are problems such as different patient patience, and body movement is not a preferable index of pain. On the other hand, an increase in amylase or its activity in a saliva sample is an objective indicator of pain in a patient, and by detecting this increase, it is possible to determine when an analgesic is required. In other words, in endoscopic submucosal dissection under conscious sedation, when an increase in salivary sample amylase or activity is detected, it is determined that it is appropriate to administer an analgesic immediately after the detection. Is done. Thus, an increase in amylase or its activity in a saliva sample is an objective indicator for determining the timing of analgesic administration.

  Since an increase in saliva sample amylase or its activity is an objective indicator for determining the timing of analgesic administration, measurement of saliva sample amylase or its activity, detection of salivary amylase or its increase in activity, and salivary amylase Alternatively, the present invention can provide a device for administering an analgesic based on an increase in its activity in a series of steps. The apparatus comprises the following main parts, characterized in that these main parts are interlocked: (i) a saliva amylase or a measurement part of its activity, (ii) a salivary amylase by comparing the measured value with a reference value Or a part that calculates the rate of change or increase in its activity, (iii) a part that displays the measured value and rate of change, and (iv) directs the automatic administration of analgesics based on the increase in salivary amylase or its activity Part (V) A part for automatically administering an analgesic. Saliva samples can be collected intermittently and sequentially added to the measuring part of the device. In addition, by inserting a saliva collection device into the oral cavity, saliva samples can be collected continuously and saliva amylase or its activity can be measured continuously.

  The present invention also provides an analgesic management device used in a sedation method, specifically a drug supply device and a notification device.

  The drug supply device according to the present invention is a saliva amylase activity measuring unit that measures amylase activity using saliva collected from a human being subjected to sedation as a specimen, and outputs measurement information indicating the measured value, and the above measurement Drug supply determination means for outputting supply information indicating supply of a drug based on information, and holding at least one of a sedative or an analgesic as a drug to be supplied, and the drug held based on the supply information described above And a medicine supply means for supplying the medicine for human administration.

  The sedation method is applied by introducing a sedative and an analgesic into a human. Saliva is collected from the mouth of a human subject to sedation using an appropriate collection tool. Saliva collection can be performed intermittently or continuously, and is preferably performed intermittently. The collected saliva is used as a specimen, and the amylase activity is measured by the salivary amylase activity measuring means. The salivary amylase activity is quantified by, for example, using a reagent that develops color by a substrate reaction with amylase in a specimen, and optically calibrating the degree of color development. The salivary amylase activity measuring means outputs a digitized measurement value (amylase activity) as measurement information, for example, as an electrical signal.

  The medicine supply determining means obtains output measurement information by being electrically connected to, for example, saliva amylase activity measuring means. The medicine supply determining means determines whether or not the medicine should be supplied based on the obtained measurement information, and outputs the supply information based on the determination that the medicine should be supplied. This supply information is output as an electrical signal, for example.

  The drug supply means holds a drug to be supplied to a human. This drug is a drug required for the sedation method, and specifically, is at least one of a sedative and an analgesic. The medicine supply means has, for example, a syringe pump, and can supply a desired amount of medicine held in the syringe. The medicine supply unit obtains the output supply information by being electrically connected to the medicine supply determination unit, for example. The medicine supply means supplies the held medicine based on the obtained supply information. This supply is performed, for example, to an infusion circuit connected to a human subjected to sedation. As a result, the medicine supplied by the medicine supply means is administered to a human subjected to sedation.

  The medicine supply determining means has a first value for determining whether or not to supply the medicine, and supplies supply information to which the medicine is to be supplied based on a comparison between the measurement information and the first threshold value. It may be output.

  In this drug supply determining means, the “threshold value” refers to a value of salivary amylase activity sufficient to determine that the patient felt pain under the sedation method. As described above, a patient's pain under sedation can be determined by detecting an increase in salivary amylase activity. Therefore, the threshold value is a value obtained by adding 20 kU / L to the above-described reference value, preferably a value obtained by adding 30 kU / L, more preferably a value obtained by adding 40 kU / L, and further preferably a value obtained by adding 50 kU / L. possible. The threshold value can be set based on the reference value after measurement. For example, the threshold value may be 20 kU / L, preferably 30 kU / L, more preferably 40 kU / L, still more preferably 50 kU / L, and still more preferably 100 kU / L.

  The medicine supply determining unit compares the measurement value included in the obtained measurement information with the first threshold, determines that the medicine should be supplied if the measurement value is equal to or greater than the first threshold, and outputs the supply information. .

  The medicine supply determining means may determine the amount of the medicine to be supplied based on the measurement value and output supply information including the amount of medicine to be supplied.

  The medicine supply determining unit has a function and a table indicating the relationship between the measured value and the medicine supply amount. The medicine supply determining means calculates the amount of medicine to be supplied from the measurement values included in the obtained measurement information based on the function and the table, and outputs the supply information. Thereby, a chemical | medical agent can be administered quantitatively based on the measured value of salivary amylase activity.

  The notification device according to the present invention measures salivary amylase activity using saliva collected from a human subject to sedation as a specimen, and outputs measurement information indicating the measurement value, and the measurement information A notification determining unit that outputs notification information indicating that notification is to be performed based on the notification information, and a notification unit that performs notification based on the notification information.

  The sedation method is applied by introducing a sedative and an analgesic into a human. Saliva is collected from the mouth of a human subject to sedation using an appropriate collection tool. The collected saliva is used as a specimen, and the amylase activity is measured by the salivary amylase activity measuring means. The salivary amylase activity is quantified by, for example, using a reagent that develops color by a substrate reaction with amylase in a specimen, and optically calibrating the degree of color development. The salivary amylase activity measuring means outputs a digitized measurement value (amylase activity) as measurement information, for example, as an electrical signal.

  For example, the notification determining unit is electrically connected to the salivary amylase activity measuring unit to obtain the output measurement information. The notification determining means determines whether or not the medicine should be supplied based on the obtained measurement information, and outputs the notification information based on the determination that the medicine should be supplied. This notification information is output as an electrical signal, for example.

  The notification means performs notification that can be sensed by the five human senses, such as sound, light, and vibration. The notification unit obtains the output notification information by being electrically connected to the notification determination unit, for example. The notification means performs notification based on the obtained notification information. This notification is sensed by a medical person monitoring the sedation method, and the medical person administers the drug to the person who has been subjected to the sedation method based on the notification.

  The notification determining means has a second threshold value for determining whether or not to perform the notification, and outputs the notification information based on a comparison between the measurement information and the second threshold value. Good.

  The notification determining unit compares the measurement value included in the obtained measurement information with the second threshold, determines that the notification should be performed if the measurement value is equal to or greater than the second threshold, and outputs the notification information.

  In this notification determining means, the “threshold value” means a value of salivary amylase activity sufficient to determine that the patient feels pain under the sedation method. As described above, a patient's pain under sedation can be determined by detecting an increase in salivary amylase activity. Therefore, the threshold value is a value obtained by adding 20 kU / L to the above-described reference value, preferably a value obtained by adding 30 kU / L, more preferably a value obtained by adding 40 kU / L, and further preferably a value obtained by adding 50 kU / L. possible. The threshold value can be set based on the reference value after measurement. For example, the threshold value may be 20 kU / L, preferably 30 kU / L, more preferably 40 kU / L, still more preferably 50 kU / L, and still more preferably 100 kU / L. .

  According to the medicine supply device or the notification device according to the present invention, the analgesic management method according to the present invention can be implemented.

  Hereinafter, the present invention will be described more specifically with reference to examples. In addition, this invention is not limited at all by the Example shown below, In the range which does not change the summary of this invention, it can change suitably.

  For patients with early gastric cancer, endoscopic submucosal dissection (hereinafter referred to as ESD) was performed under conscious sedation or general anesthesia, and changes in saliva amylase activity during the operation were measured. In addition, a patient questionnaire was conducted postoperatively to compare and evaluate patient stress due to differences in anesthesia. This example was implemented after confirming the patient's intention by performing informed consent.

  ESD was performed on 26 patients with early gastric cancer (Table 1). Of the 26 cases, 16 cases were performed under conscious sedation (hereinafter referred to as Group D), and 10 cases were performed under general anesthesia (hereinafter referred to as Group G) (FIG. 1). Group D introduces sedation by intravenous administration of midazolam 2.5-3.5 mg and pentazocine 7.5 mg (hereinafter sometimes abbreviated as iv), followed by midazolam Was administered intravenously at 2.5 to 3.5 mg / h to maintain a sedative state, and an analgesic state was maintained by appropriately administering pentazocine. Group G introduced anesthesia by intravenous administration of propofol 0.5 mg / kg / 10 min and fentanyl 0.1 mg, and then maintained the anesthesia with sevoflurane. The evaluation of the sedation state was performed by measuring a bispectral index (hereinafter sometimes referred to as BIS) using a BIS monitor (manufactured by ASPECTS MEDICAL). The BIS monitor is a device that detects a sedation state by quantifying the process until the electroencephalogram change, that is, the fast wave at the time of awakening, becomes a high-amplitude slow wave by an anesthetic and finally flattenes. The maximum blood pressure (sometimes abbreviated as BPmax) and the pulse rate (sometimes abbreviated as PR) were measured.

  Salivary amylase activity was measured before ESD, after introduction to sedation or anesthesia, and at 30 minute intervals during ESD, and also several hours after the end of ESD and before discharge (FIG. 1). . Saliva was collected from the patient's tongue. The salivary amylase activity was measured using a salivary amylase monitor (manufactured by Nipro Corporation). The time required for obtaining the measurement result of salivary amylase activity from saliva collection is about 1 minute.

  The changes in salivary amylase activity in Group D and Group G before, during and after surgery are shown in FIGS. FIG. 2 shows the absolute value of salivary amylase activity, and FIG. 3 shows the relative value of salivary amylase change. The salivary amylase activity of Group D was about 45 kU / L the day before ESD, but decreased to about 20 kU / L after anesthesia, gradually increased from 30 minutes after the start of ESD, and reached about 120 kU / L after 150 minutes. And then decreased. On the other hand, the salivary amylase activity of Group G was about 70 kU / L on the day before ESD, indicating a lower value in both measurements after anesthesia and during ESD.

  FIG. 4 shows changes in salivary amylase activity before and during surgery in a representative case of Group D cases. In this case, the sedation during the operation was well maintained, as is apparent from the BIS monitor values. On the other hand, salivary amylase activity was almost 0 kU / L at the start of ESD, but increased to about 250 kU / L 60 minutes after the start of ESD. Therefore, when the analgesic agent pentazocine 7.5 mg was intravenously administered and the salivary amylase activity was measured immediately after that, the activity decreased to the same level as at the start of ESD, and remained at about 0 kU / L until 120 minutes after the start of ESD. . However, since salivary amylase activity increased to about 200 kU / L 150 minutes after the start of ESD, when 7.5 mg of pentazocine was intravenously administered, the activity decreased to the same level as at the start of ESD.

  Thus, salivary amylase activity increased during ESD under conscious sedation, and the increased salivary amylase activity was significantly reduced by administration of the analgesic agent. Can be considered to reflect that the patient's effect is reduced, thereby causing the patient to feel pain. That is, an increase in salivary amylase activity during ESD under conscious sedation can be used as an index for detecting pain in a patient and evaluating analgesia with an analgesic.

  Table 2 shows the results of the patient questionnaire. Table 2 revealed that about 44% of patients who received ESD under conscious sedation felt some kind of stress.

  As described above, it can be considered that the stress of patients undergoing ESD under conscious sedation is due to the pain caused by the reduction of the analgesic effect by the analgesic. By measuring salivary amylase activity and detecting an increase in the activity, the patient's pain can be detected and an appropriate time to administer the analgesic can be determined. Thus, by measuring salivary amylase activity, it is possible to manage analgesia of the patient during the procedure, and as a result, it is possible to reduce the patient's stress.

  Below, the chemical | medical agent supply apparatus 10 which concerns on 1st Embodiment of the analgesic management apparatus which concerns on this invention is demonstrated.

  As FIG. 5 shows, the chemical | medical agent supply apparatus 10 makes the saliva amylase monitor 11, the computer 12, and the syringe pump 13 the main structures. The saliva amylase monitor 11 and the computer 12, and the computer 12 and the syringe pump 13 are electrically connected so as to be able to communicate information composed of electronic signals. These connections are realized by a predetermined communication standard such as a LAN. The salivary amylase monitor 11 corresponds to the salivary amylase activity measuring means according to the present invention, the computer 12 corresponds to the medicine supply determining means, and the syringe pump 13 corresponds to the medicine supplying means.

  The saliva amylase monitor 11 measures the amylase activity contained in the saliva using saliva collected from a human as a specimen, and outputs measurement information indicating the measurement value. The salivary amylase monitor 11 includes a main body 14 and a sample collection unit 15 as main components.

  The sample collection unit 15 is for collecting the saliva of the human 16 subjected to the sedation method, and a material and shape capable of collecting and holding the saliva are employed. The sample collection unit 15 can be inserted into and removed from the main body 14 such that the side on which the saliva is held is inserted into the main body 14.

  The main body 14 holds a reagent capable of measuring amylase activity. When the sample collection unit 15 holding saliva is inserted into the main body 14, the reagent in the main body 14 and the saliva held in the sample collection unit 15 come into contact and react. The reagent generates a color source body by, for example, an enzymatic reaction.

  The main body 14 incorporates a color discrimination sensor that optically measures a color source generated by the reaction of the reagent. This color discrimination sensor outputs the measured optical quantity as an electronic signal. The main body 14 can digitize this electronic signal as an amylase activity value and display it on a display, and can output it to an external information device through an interface. The amylase activity value output from the main body 14 corresponds to the measurement information in the present invention.

  An example of the saliva amylase monitor 11 described above is disclosed in Japanese Patent Application Laid-Open Nos. 2004-267202, 2004-24236, and 2004-121214 (Patent Documents 1 to 3).

  Although not shown in each figure, the computer 12 has a CPU, a ROM, and a RAM as a control unit, and this control unit is connected to a LAN I / F (Local Area Network Interface) and a HDD (Hard Disk Drive) via a bus. The keyboard, mouse and display are communicably connected.

  The ROM of the control unit stores a program and the like for determining whether the CPU should supply a drug based on the amylase activity value and the supply amount. The RAM is used as a storage area or a work area for temporarily storing various data used when the CPU executes this program.

  The LAN I / F is an interface that connects the computer 12 to the saliva amylase monitor 11 and the syringe pump 13 in a communicable manner. The HDD stores programs for the CPU to execute various processes based on information input from a keyboard or the like. The keyboard and mouse receive operation inputs such as operation instructions and settings for the control unit. The display displays various screen information.

  The control unit of the computer 12 stores a program for determining whether or not to supply a drug based on the amylase activity value and determining the amount of drug to be supplied. In this program, a threshold for determining whether or not to supply a medicine is set. Since the amylase activity value in the saliva of the human 16 subjected to the sedation method is almost zero, for example, 50 to 100 kU / L can be set as the threshold value. When the program receives the amylase activity value output from the salivary amylase monitor 11, the program compares whether the amylase activity value is greater than or equal to a threshold value. If the amylase activity value is greater than or equal to the threshold value, supply information for supplying the drug is output as an electronic signal. This threshold corresponds to the first threshold in the present invention.

  The above-described program calculates the amount of drug to be supplied on condition that the received amylase activity value is equal to or greater than a threshold value. In the program, a table is set in which the amylase activity value equal to or greater than the above-mentioned threshold is set to a predetermined numerical range, and the drug amount corresponding to each numerical range is set. The numerical range is divided, for example, every 50 kIU / L. The amount of drug to be supplied is set to increase in proportion to the amylase activity value. If the amylase activity value received from the salivary amylase monitor 11 is one or more of the above-mentioned colors, the program determines which numerical range the amylase activity value belongs to and uses the numeric value range to which it belongs. The amount of medicine to be supplied corresponding to the amount of medicine is included in the supply information described above and output. The amount of drug to be supplied may be calculated based on a function of the amylase activity value and the amount of drug instead of such a table. If there are a plurality of medicines to be supplied, the supply amount is calculated for each medicine.

  The syringe pump 13 outputs a drive signal to each actuator based on the syringes 17 and 18 filled with a medicine to be used for the sedation, an actuator (not shown) that drives the plunger of each syringe 17 and 18, and supply amount information. And a control unit. Syringes 17 and 18 are filled with sedatives or analgesics used for sedation. When the control unit receives the supply information described above, the control unit determines whether or not the supply information includes a command to supply each medicine. Based on this, a drive signal indicating the drive amount of the actuator is output, and each medicine is discharged from each syringe 17, 18. Each syringe 17, 18 has a liquid channel 19, 20 formed by connecting a tube or the like to the tip of the syringe 17, an infusion circuit or the like in which the liquid channel 19, 20 is connected to a vein of a human 16 or the like. For example, they are connected via a three-way cock. Accordingly, each medicine that has flowed out of the syringes 17 and 18 is administered to the human 16 through the liquid channels 19 and 20 and the infusion circuit.

  Hereinafter, a medicine supply method using the medicine supply apparatus 10 described above will be described.

  A sedation method is applied to the human 16 to be subjected to a desired operation or the like. This sedation is applied by putting a sedative and an analgesic into human 16.

  As shown in FIG. 6, saliva is collected from the mouth of a human 16 that has been subjected to sedation using the sample collection unit 15 (S1). The saliva collection may be performed using another collection tool, and the collected saliva may be transferred to the sample collection unit 15. The timing for collecting saliva is, for example, every 30 minutes after the sedation is applied.

  After collecting saliva, the sample collection unit 15 is inserted into the main body 14 of the saliva amylase monitor 11 and the amylase activity value is measured (S2). The saliva amylase monitor 11 outputs the measured value to the computer 12 when the amylase activity value is measured.

  When receiving the measurement value, the computer 12 determines whether or not the medicine should be supplied in contrast to the threshold value as described above (S3). If further medicine should be supplied (S3: Y). The supply amount of the medicine is calculated (S4). Then, supply information indicating these is output to the syringe pump 13. If the measured value is less than the threshold value described above, the computer 12 ends the operation without outputting the supply information (S3: N).

  When the syringe pump 13 receives the supply information, the syringe pump 13 drives the actuator to supply the medicine with the command to be supplied, that is, the sedative or the analgesic, in the supply amount included in the supply information. The medicine is discharged from 18 (S5). The discharged drug is administered to the human 16 through the liquid flow paths 19 and 20 and the infusion circuit.

  As described above, according to the drug supply device according to the present embodiment, the amylase activity in saliva collected from the sedated human 16 is measured, and the drug should be supplied based on this amylase activity value. Since the medicine required for the sedation method is supplied, the drug is automatically administered when the human 16 who has been subjected to the sedation feels pain, and the amnestic effect is enhanced. Thereby, control of a sedation method is performed simply.

  Further, since the computer 12 calculates the amount of drug to be supplied based on the amylase activity value and outputs supply information including the amount of drug to be supplied, the drug is quantitatively administered based on the measured value of the salivary amylase activity. can do.

  Below, the alerting | reporting apparatus 30 which concerns on 2nd Embodiment of the analgesic management apparatus which concerns on this invention is demonstrated.

  As shown in FIG. 7, the notification device 30 mainly includes a saliva amylase monitor 11, a computer 12, and a buzzer 31. The saliva amylase monitor 11 and the computer 12, and the computer 12 and the buzzer 31 are electrically connected so that information composed of electronic signals can be communicated. These connections are realized by a predetermined communication standard such as a LAN. The saliva amylase monitor 11 corresponds to saliva amylase activity measuring means according to the present invention, the computer 12 corresponds to notification determining means, and the buzzer 12 corresponds to notification means.

  The saliva amylase monitor 11 measures the amylase activity contained in the saliva using saliva collected from a human as a specimen, and outputs measurement information indicating the measurement value. The salivary amylase monitor 11 includes a main body 14 and a sample collection unit 15 as main components. Since the salivary amylase monitor 11 is the same as that of the first embodiment described above, detailed description thereof is omitted here.

  The computer 12 includes a CPU, a ROM, and a RAM as a control unit, and the control unit is configured to be communicably connected to a LAN I / F, HDD, keyboard, mouse, and display via a bus. The computer 12 is the same as the first embodiment described above except that the installed program is different. Therefore, only the different parts are described in detail, and other detailed descriptions are omitted.

  The control unit of the computer 12 stores a program for determining whether to perform notification based on the amylase activity value. In this program, a threshold for determining whether to perform notification is set. Since the amylase activity value in the saliva of the human 16 subjected to the sedation method is almost zero, for example, 50 to 100 kU / L can be set as the threshold value. When the program receives the amylase activity value output from the salivary amylase monitor 11, the program compares whether the amylase activity value is greater than or equal to a threshold value. If the amylase activity value is greater than or equal to the threshold value, notification information to be notified is output as an electronic signal. This threshold corresponds to the second threshold in the present invention.

  When the buzzer 31 receives the notification information, the buzzer 31 oscillates as a warning sound. Although not shown in the figure, the buzzer 31 is provided with a stop button, and when the stop button is pressed, the buzzer 31 stops oscillation of the buzzer sound. The buzzer 31 may be provided integrally with the computer 12. Further, instead of the buzzer 31, a light that emits light, a vibrator that emits vibration, or the like may be used, or a combination of these may be used.

  Hereinafter, a medicine supply method using the above-described notification device 30 will be described.

  A sedation method is applied to the human 16 to be subjected to a desired operation or the like. This sedation is applied by putting a sedative and an analgesic into human 16.

  As shown in FIG. 8, saliva is collected from the mouth of a human 16 subjected to sedation using the sample collection unit 15 (S11). The saliva collection may be performed using another collection tool, and the collected saliva may be transferred to the sample collection unit 15. The timing for collecting saliva is, for example, every 30 minutes after the sedation is applied.

  After collecting the saliva, the sample collection unit 15 is inserted into the main body 14 of the saliva amylase monitor 11 and the amylase activity value is measured (S12). The saliva amylase monitor 11 outputs the measured value to the computer 12 when the amylase activity value is measured.

  When receiving the measurement value, the computer 12 determines whether or not to perform notification in comparison with the threshold value as described above (S13). The computer 12 outputs notification information to the buzzer 31 if the measurement value is equal to or greater than the above-described threshold value (S13: Y), and ends the operation without outputting the notification information if the measurement value is less than the above-described threshold value. (S13: N).

  When receiving the notification information, the buzzer 31 oscillates a buzzer sound (S14). As a result, the medical staff monitoring the sedation knows that it is time to administer the drug to the human 16. And the medical staff who heard the buzzer sound can administer a drug, that is, a sedative or an analgesic, to the human 16 who has been subjected to the sedation at an appropriate timing.

  As described above, according to the notification device 30 according to the present embodiment, should the amylase activity in saliva collected from the sedated human 16 be measured, and notification be made based on the amylase activity? Therefore, a medical person can administer a drug required for the sedation method to the human 16 based on the notification. As a result, the amnestic effect is enhanced and the sedation method is performed. The pain of human 16 is removed. Thereby, control of a sedation method is performed simply.

It is a figure which shows the time of salivary amylase activity measurement during the period from the hospitalization of an early gastric cancer patient who received endoscopic submucosal dissection (ESD) to discharge. It is a figure which shows the salivary amylase activity before enforcement during ESD enforcement. Group D shows an ESD-executed group (16 cases) under conscious sedation, and Group G shows an ESD-executed group (10 cases) under anesthesia. The symbols “■” and “♦” indicate the D group and the G group, respectively. A value shows the average value of each case. The symbols “*” and “**” indicate significant differences P <0.01 and P <0.05, respectively. It is a figure which shows the rate of change of the salivary amylase activity before, during and after ESD. Group D shows an ESD-executed group (16 cases) under conscious sedation, and Group G shows an ESD-executed group (10 cases) under anesthesia. The symbols “■” and “♦” indicate the D group and the G group, respectively. A value shows the average value of each case. The symbols “*” and “**” indicate significant differences P <0.01 and P <0.001, respectively. It is a figure which shows the salivary amylase activity in the ESD execution case under the conscious sedation method. In this case, sedation was introduced by intravenous administration (iv) of midazolam and pentazocine, and then sedation was maintained with midazolam and pentazocine was administered as appropriate. In the figure, symbol “♦” indicates salivary amylase activity, symbol “■” indicates bispectral index (BIS) indicating sedation, symbol “▲” indicates systolic blood pressure (BPmax), and symbol “●” indicates pulse rate ( PR). It is a lineblock diagram showing the composition of medicine supply device 10 concerning a 1st embodiment of the present invention. 3 is a flowchart showing a medicine supply method using the medicine supply apparatus 10. It is a block diagram which shows the structure of the alerting | reporting apparatus 30 which concerns on 2nd Embodiment of this invention. 5 is a flowchart showing a medicine supply method using the notification device 30.

Explanation of symbols

10 ... Drug supply device 11 ... Salivary amylase monitor (saliva amylase activity measuring means)
12 ... Computer (medicine supply determining means, notification determining means)
13 ... Syringe pump (medicine supply means)
14 ... Body 15 of saliva amylase monitor 11 ... Sample collection part 16 of saliva amylase monitor 11 ... Human 17 ... Syringe 18 ... Syringe 19 ... Liquid flow path 20 ... Liquid flow Road 30 ... notification device 31 ... buzzer (notification means)

Claims (24)

A method for detecting pain in endoscopic submucosal dissection under conscious sedation, comprising measuring amylase in saliva samples collected intermittently or continuously and detecting an increase in salivary amylase. The method according to claim 1, wherein the saliva sample is a saliva sample collected intermittently. The method according to claim 1 or 2, wherein measuring amylase in a saliva sample and detecting an increase in salivary amylase is measuring an amylase activity in the saliva sample and detecting an increase in salivary amylase activity. The method according to claim 3, wherein the increase in salivary amylase activity is an increase of 20 kU / L or more compared to the salivary amylase activity before the treatment. The method according to any one of claims 1 to 4, wherein the conscious sedation is introduced by intravenous administration of midazolam and pentazocine. The method according to any one of claims 1 to 5, wherein the endoscopic submucosal dissection is endoscopic submucosal dissection for gastric cancer. Midazolam and pentazocine characterized by measuring amylase activity of a saliva sample collected intermittently and detecting an increase in salivary amylase activity of 20 kU / L or more compared to the salivary amylase activity before treatment A method for detecting pain in endoscopic submucosal dissection with conscious sedation introduced by intravenous administration of (pentazocine). When amylase activity is measured in saliva samples collected intermittently or continuously, and an increase in salivary amylase activity is detected, an analgesic administered in endoscopic submucosal dissection under conscious sedation A method for evaluating the analgesic level of an analgesic agent in endoscopic submucosal dissection under conscious sedation, wherein the analgesic level is determined to have decreased. The method according to claim 8, wherein the amylase activity of the saliva sample collected intermittently is measured. The method according to claim 8 or 9, wherein measuring amylase in a saliva sample and detecting an increase in salivary amylase is measuring an amylase activity in the saliva sample and detecting an increase in salivary amylase activity. The method according to claim 10, wherein the increase in salivary amylase activity is an increase of 20 kU / L or more compared to the salivary amylase activity before treatment. The method according to any one of claims 8 to 11, wherein the conscious sedation is introduced by intravenous administration of midazolam and pentazocine. The method according to any one of claims 8 to 12, wherein the endoscopic submucosal dissection is endoscopic submucosal dissection for gastric cancer. Endoscopic conscious sedation, characterized by measuring amylase activity in intermittent or continuously collected saliva samples and determining the administration of analgesics by detecting increased salivary amylase activity Analgesic management method in submucosal dissection. The method according to claim 14, wherein the amylase activity of the saliva sample collected intermittently is measured. The method according to claim 14 or 15, wherein measuring amylase in a saliva sample and detecting an increase in salivary amylase is measuring an amylase activity in the saliva sample and detecting an increase in salivary amylase activity. The method according to claim 16, wherein the increase in salivary amylase activity is an increase of 20 kU / L or more compared to the salivary amylase activity before the treatment. The method according to any one of claims 14 to 17, wherein the conscious sedation is introduced by intravenous administration of midazolam and pentazocine. The method according to any one of claims 14 to 18, wherein the endoscopic submucosal dissection is endoscopic submucosal dissection for gastric cancer.   Saliva amylase activity measuring means for measuring amylase activity using saliva collected from a human being subjected to sedation as a specimen, and outputting measurement information indicating the measured value, and supply of a drug based on the measurement information Drug supply determining means for outputting supply information, and drug supply for holding at least one of sedative or analgesic as a drug to be supplied and supplying the held drug based on the supply information to the human A medicine supply device comprising: means.   The medicine supply determining means has a first threshold value for determining whether or not to supply the medicine. Based on the comparison between the measurement information and the first threshold value, supply information for supplying the medicine is obtained. The medicine supply device according to claim 20, which outputs the medicine supply device.   The medicine supply apparatus according to claim 20 or 21, wherein the medicine supply determining means determines an amount of the medicine to be supplied based on the measurement value, and outputs supply information including the amount of medicine to be supplied.   A saliva amylase activity measuring means for measuring amylase activity using saliva collected from a human subject to sedation as a specimen and outputting measurement information indicating the measured value, and indicating that the information should be reported based on the measurement information A notification device comprising: notification determination means for outputting notification information; and notification means for performing notification based on the notification information.   The said notification determination means has a 2nd threshold value for determining whether the said notification is performed, The said notification information is output based on contrast with the said measurement information and the said 2nd threshold value. Informing device.

Images