Medicines for intravenous sedation

Abstract

To provide an intravenous sedative for dental treatment and oral surgery that balances avoidance of respiratory depression, sleep state, and amnesia. [Solution] A pharmaceutical product is provided for use in combination with propofol in a method of inducing sedation in a human subject during dental treatment or oral surgery, wherein the pharmaceutical product contains dexmedetomidine, and the method of inducing sedation in the subject includes the following: (1-1) For patients with a BMI of 22 or higher, a loading procedure is performed before the start of the procedure, in which 3-6 μg / kg / h of dexmedetomidine is administered intravenously for approximately 10 minutes based on ideal body weight. (1-2) If the BMI is less than 22, a loading process is performed before the start of the procedure, in which 3-6 μg / kg / h of dexmedetomidine based on actual body weight is administered intravenously for about 10 minutes, and (2) After the loading process, sedation is maintained by intravenously administering dexmedetomidine at a rate of 0.2-0.5 μg / kg / h based on actual body weight and propofol to a blood concentration of 0.4-0.8 μg / ml based on actual body weight, and the procedure is performed under the sedated state.

Description

TECHNICAL FIELD

[0001] The present invention relates to a medicament for intravenous sedation combined with intravenous anesthesia. More specifically, the present invention relates to a medicament useful for intravenous sedation during dental treatment or oral surgery.

BACKGROUND ART

[0002] In dental treatment, particularly in oral surgery including tooth extraction and implant placement, not only analgesia using drugs to relieve pain, but also sedation is performed in which patient management is carried out using drugs to minimize fear, anxiety and tension toward the surgery, and suppress harmful reflexes during the surgery, so that the treatment can be performed comfortably and safely. Furthermore, in the dental field where the surgical field and the airway are aligned, and treatments are performed under water irrigation in the oral cavity during oral surgery, it is needless to say that there is a higher necessity to maintain consciousness than in other fields in terms of airway management and aspiration prevention management.

[0003] Conventionally, in the field of dental treatment, particularly oral surgery in dentistry, a method called intravenous sedation combined with intravenous anesthesia or intravenous sedation, in which propofol and midazolam are intravenously administered, has been adopted. However, in the intravenous sedation method using a combination of propofol and midazolam, it is often extremely difficult to achieve a proper balance of respiratory state, sleep state, and amnesic effect respectively. Particularly when the patient has a poor respiratory condition such as obesity or is a COPD patient, during intravenous sedation, in consideration of safety and to avoid hypoxic conditions, sedation is often performed while abandoning the acquisition of sleep and amnesic effects, which increases the burden on the patient.

SUMMARY OF THE INVENTION

PROBLEMS TO BE SOLVED BY THE INVENTION

[0004] The present application aims to provide a medicament for intravenous sedation in dental treatment and oral surgery. More specifically, the present application aims to provide a medicament for intravenous sedation for dental treatment and oral surgery, which avoids respiratory depression and achieves a well-balanced state of sleep and amnesic effect. [Means for solving the problem]

[0005] This application provides a pharmaceutical product used in combination with propofol in a method for inducing sedation in a human subject during dental treatment or oral surgery, wherein the pharmaceutical product comprises dexmedetomidine, and the method for inducing sedation in the subject includes the following: (1-1) For patients with a BMI of 22 or higher, a loading procedure is performed before the start of the procedure, in which 3-6 μg / kg / h of dexmedetomidine is administered intravenously for approximately 10 minutes based on ideal body weight. (1-2) If the BMI is less than 22, a loading process is performed before the start of the procedure, in which 3-6 μg / kg / h of dexmedetomidine based on actual body weight is administered intravenously for about 10 minutes, and (2) After the loading process, sedation is maintained by intravenously administering dexmedetomidine at a rate of 0.2-0.5 μg / kg / h based on actual body weight and propofol to a blood concentration of 0.4-0.8 μg / ml based on actual body weight, and the procedure is performed under the sedated state.

[0006] The present invention also provides a pharmaceutical product used in combination with dexmedetomidine in a method for inducing sedation in a human subject during dental treatment or oral surgery, wherein the pharmaceutical product comprises propofol, and the method for inducing sedation in the subject includes the following: (1-1) For patients with a BMI of 22 or higher, a loading procedure is performed before the start of the procedure, in which 3-6 μg / kg / h of dexmedetomidine is administered intravenously for approximately 10 minutes based on ideal body weight. (1-2) For patients with a BMI of less than 22, a loading process is performed before the start of the procedure, in which 3-6 μg / kg / h of dexmedetomidine based on body weight is administered intravenously for approximately 10 minutes, and (2) After loading, sedation is maintained by intravenous administration of dexmedetomidine at a rate of 0.2-0.5 μg / kg / h based on actual body weight, and propofol, so that the blood concentration is 0.4-0.8 μg / ml based on actual body weight, and the procedure is performed under the sedated state.

[0007] The inventors have found that, particularly in oral surgery in the dental field, when suturing requires a relatively long time, such as implant placement, tooth extraction, bone regeneration induction, exostoses, removal of foreign bodies in the jawbone (so-called pin removal: removal of screws, etc.), anchor bolt placement, necrotic bone removal, partial alveolar bone resection, hematoma resection, tongue tumor resection (including leukoplakia and lichen planus), buccal mucosa tumors, removal of foreign bodies in the maxillary sinus, apicoectomy, and alveolar bone shaping, stopping the administration of dexmedetomidine after the completion of highly invasive procedures, for example after the completion of the implant placement process and at the start of suturing, and managing sedation with propofol alone can lead to rapid recovery after the surgery. In other words, the pharmaceutical product of the present invention is further preferably used in the following method, which includes the step of stopping the administration of dexmedetomidine at the start of the suturing step of oral surgery and performing the suturing step under sedation by intravenously administering propofol so that its blood concentration is 0.4-0.8 μg / ml based on actual body weight.

[0008] The inventors have named the method for inducing sedation with the present invention the "DPC method," abbreviated as "Dexmedetomidine and Propofol Combination Method." [Brief explanation of the drawing]

[0009] [Figure 1] Anesthesia record for Case 1 [Figure 2] Anesthesia record for Case 2 [Figure 3] Anesthesia record for Case 3 [Figure 4] Anesthesia record for Case 4 [Figure 5] Anesthesia record for Case 5 [Figure 6] Anesthesia record for Case 6 [Figure 7] Anesthesia record for Case 7 [Figure 8] Anesthesia record for Case 8 [Figure 9-1] Anesthesia record for Case 9-1 [Figure 9-2] Anesthesia record for Case 9-2 [Figure 9-3] Anesthesia record of Case 9-3 [Figure 10-1] Anesthesia record of Case 10-1 [Figure 10-2] Anesthesia record of Case 10-2 [Figure 11] Anesthesia record of Case 11 [Figure 12] Anesthesia record of Case 12 [Figure 13] Anesthesia record of Case 13 [Figure 14] Anesthesia record of Case 14 [Figure 15] Anesthesia record of Case 15 [Figure 16-1] Anesthesia record of Case 16-1 [Figure 16-2] Anesthesia record of Case 16-2 [Figure 17] Anesthesia record of Case 17 [Figure 18] Comparison between DPC method and MP method: Heart Rate (HR) [Figure 19] Comparison between DPC method and MP method: Systolic Blood Pressure [Figure 20] Comparison between DPC method and MP method: SpO2 [Figure 21] Comparison between DPC method and MP method: Cough [Figure 22] Comparison between DPC method and MP method: Body Movement

Modes for Carrying Out the Invention

[0010] In the present application, the target sedation depth corresponds to "Moderate Sedation" in the "Guidelines for Sedation / Analgesia by Non-Anesthesiologists" (American Society of Anesthesiologists, 2002) shown in Table 1 below.

[0011]

Table 1

[0012] In this application, dexmedetomidine is used as dexmedetomidine and its salts, with dexmedetomidine hydrochloride being particularly preferred. As dexmedetomidine hydrochloride, a commercially available product containing 200 μg of dexmedetomidine per vial can be used. Hereafter, unless otherwise specified, "dexmedetomidine" includes "dexmedetomidine hydrochloride," and the amount of dexmedetomidine refers to the amount of dexmedetomidine even when dexmedetomidine hydrochloride is used.

[0013] In this application, commercially available propofol may be used. A commercially available emulsion injection solution containing 1% propofol can be used.

[0014] In this application, dexmedetomidine and propofol can be administered using devices that have been conventionally used for intravenous sedation. For example, they can be administered intravenously using an intravenous sedation pump that allows for continuous administration while controlling the dosage.

[0015] In the present specification and claims, “surgery” means making an incision in the affected area using surgical instruments or scalpels and performing therapeutic procedures. In the present specification and claims, "oral surgery" includes, but is not limited to, procedures that fall under the category of dental treatment, but examples include tooth extraction, guided bone regeneration, exostodectomy, removal of foreign bodies from the jawbone (so-called pin removal: removal of screws, etc.), anchor bolt placement, removal of necrotic bone, partial alveolar bone resection, hematoma resection, tongue tumor resection (including leukoplakia and lichen planus), buccal mucosal tumors, removal of foreign bodies from the maxillary sinus, apicoectomy, alveolar bone shaping, and dental implant placement. Furthermore, in the present specification and claims, “methods for inducing sedation” also include sedation during surgical wound dressing changes and disinfection, oral or nasal tracheal intubation, and dental treatment. In this disclosure, "procedure" means any invasive procedure in the oral surgery or dental treatment described above, other than the initiation of intravenous sedation and the administration of local anesthesia.

[0016] In the present specification and claims, "suturing process" refers only to the process of suturing performed after the completion of highly invasive procedures such as implant placement.

[0017] In this application, intravenous sedation includes a loading step and a sedation-maintaining procedure step, in which decusmedetomidine and propofol are administered in a specified combination and according to a specified dosage and administration schedule in each step.

[0018] During the loading phase, if the patient's BMI is 22 or higher, dexmedetomidine is administered intravenously for approximately 10 minutes at a dose of 3-6 μg / kg / h based on ideal body weight before the start of the procedure. If the patient's BMI is less than 22, dexmedetomidine is administered intravenously for approximately 10 minutes at a dose of 3-6 μg / kg / h based on actual body weight before the start of the procedure. This loading phase brings the blood concentration of dexmedetomidine to a level equivalent to that of a continuous infusion of 0.7 μg / kg / h.

[0019] After the loading phase, the procedure proceeds to the sedation-maintained treatment phase. During the sedation-maintained treatment phase, dexmedetomidine is administered at a continuous infusion rate of 0.2-0.5 μg / kg / h based on actual body weight, and propofol is administered intravenously to achieve an effect-site blood concentration of 0.4-0.8 μg / ml calculated from actual body weight, thereby maintaining sedation. After the maintenance phase begins, the procedure, such as oral surgery, is initiated.

[0020] Regarding the dosage of dexmedetomidine, the "ideal weight standard" refers to the dosage determined based on the ideal weight calculated from the patient's height. Here, "ideal weight" is defined as a BMI of 22 kg / m² relative to the patient's height. 2 This refers to the weight calculated based on the settings.

[0021] Furthermore, in this disclosure, "expected weight" refers to the weight calculated as follows: Expected weight for men = 50 + 0.9 (height (cm) - 152.4), and Expected weight for women = 45.5 + 0.91 × (height (cm) - 152.4).

[0022] Regarding the dosage of dexmedetomidine and propofol, "based on actual body weight" or "actual body weight" refers to the dosage determined based on the patient's actual body weight.

[0023] Site-of-effect blood concentration refers to the propofol blood concentration in the central nervous system, specifically in brain tissue. Control of site-of-effect blood concentration can be performed under the control of a device that stores the drug dosage, calculates the site-of-effect blood concentration based on the patient's weight, and controls the administration rate.

[0024] Dexmedetomidine and propofol can be administered using devices commonly used for intravenous sedation. For example, they can be administered using syringe infusion pumps or infusion devices equipped with infusion pumps that allow for appropriate control of the administration rate.

[0025] During procedures performed under intravenous sedation, patients are generally kept under continuous monitoring of vital signs such as heart rate, respiratory rate, oxygen saturation, and blood pressure, as is done during sedation anesthesia. If respiratory deterioration is anticipated, oxygen administration via nasal cannula or nasal high-flow may be used in combination.

[0026] In implementing the intravenous sedation method of this invention, a syringe infusion pump device and an infusion pump device connected to the medical AI system can be used. The medical AI system can also be connected to a nasal cannula and an oxygen delivery device. By inputting the patient's vital signs (height, weight, age, heart disease, blood test results, urine test results, etc.) and real-time vital information into the medical A1 system, the AI ​​system can calculate the optimized blood concentration of anesthetic drugs and their administration rates, and manage the patient, thereby enabling the safe implementation of intravenous sedation.

[0027] Examples of procedures to which the intravenous sedative drug of the present invention is applied include tooth extraction, bone regeneration induction, bone exostosum resection, removal of foreign bodies in the jawbone (so-called pin removal: removal of screws, etc.), anchor bolt placement, necrotic bone removal, partial alveolar bone resection, hematoma resection, tongue tumor resection (including leukoplakia and lichen planus), buccal mucosal tumors, removal of foreign bodies in the maxillary sinus, sedation during wound dressing changes and disinfection, sedation during oral or nasal tracheal intubation, and so-called dental treatment. Examples of oral surgery include tooth extraction of a few teeth, hematoma resection with a small surgical area, tongue tumor resection (including leukoplakia and lichen planus), and Procedures such as buccal mucosal tumor resection do not require sutures or require relatively short suturing times. However, after highly invasive procedures such as implant placement, the suturing process may take a relatively long time.

[0028] The first aspect of the present invention is applicable to surgeries in which suturing is not required after a highly invasive procedure, or in which suturing is completed in a relatively short time, for example, within 15 minutes. In the first aspect of the present invention, the administration of decusmimetomidine and propofol during the sedation-maintained procedure is continued until the end of the surgery, including the suturing process. The administration of decusmimetomidine and propofol during the sedation-maintained procedure may be terminated simultaneously after the end of the surgery, or, for operational convenience, one may be terminated a few minutes after the other, for example, within 5 minutes, or for example, within 3 minutes.

[0029] The second aspect of this application applies to procedures that include suturing after highly invasive and painful procedures, such as implant placement, bone regeneration induction, bone exostosis resection, removal of foreign bodies in the jawbone (so-called pin removal: removal of screws, etc.), anchor bolt placement, necrotic bone removal, partial alveolar bone resection, and removal of foreign bodies in the maxillary sinus, where suturing is performed for a relatively long time, for example, exceeding 15, 30, 60, or 90 minutes, up to about 120 minutes, after a highly invasive procedure. In the second aspect of this application, when the highly invasive procedure is completed during the sedation-maintained procedure and the suturing process begins, the administration of dexmedetomidine is stopped, and propofol is administered intravenously to maintain a blood concentration of 0.4-0.8 μg / ml based on actual body weight, and the suturing process is performed under sedation. By stopping the administration of dexmedetomidine first and maintaining sedation with propofol alone, it is possible to shorten the postoperative recovery time.

[0030] In the present specification and claims, "suturing process" refers to the process of suturing performed after highly invasive procedures such as incision, tooth extraction, apicoectomy, alveolar bone shaping, and implant placement have been completed in surgery, etc. In this application, even if suturing is performed in parallel with a highly invasive procedure, the period during which the highly invasive procedure is being performed in parallel is not referred to as the "suturing process."

[0031] In this application, after the loading process, the sedation procedure is limited to a maximum of approximately 4 hours, preferably up to 3 hours, and more preferably up to 2 hours.

[0032] The suturing step in the second embodiment of the present application is performed so as to be completed within a maximum of about 120 minutes, preferably 60 minutes, and more preferably 30 minutes. After the suturing step is completed, the administration of propofol is stopped.

[0033] The second aspect of this invention is particularly effective when applied after highly invasive procedures, especially those involving suturing, such as outpatient surgery or when there is a strong abnormal constriction reflex and maintenance with propofol alone is effective. Furthermore, patients with a BMI exceeding 30, who have difficulty managing their airways, or those with so-called respiratory failure (including sleep apnea), take a particularly long time to recover from sedation. In such patients, the second aspect of this invention is suitably used.

[0034] In the intravenous sedation method of this invention, local anesthesia is administered as needed according to the type of procedure. The drugs and concentrations used for local anesthesia should follow conventionally known guidelines.

[0035] The pharmaceutical product of this application is applicable to all patients requiring intravenous sedation during dental treatment or oral surgery. In particular, it can be used to induce appropriate intravenous sedation in obese patients with a BMI of 25 or higher, and in severely obese patients with a BMI exceeding 30. [Examples]

[0036] The following are cases in which intravenous sedation was administered to patients undergoing dental treatment or oral surgery. Hereafter, dexmedetomidine will be referred to as "DEX" and propofol as "Pro". In each case, the following criteria were used to evaluate choking, body movement, the need for atropine, and the need for vasopressors.

[0037] [Table 2]

[0038] <Case 1> Patient: HK Age: 40 Gender: Female Height: 149.8m Weight: 89.3kg BMI: 39.77 Procedure: 6. Tooth Extraction Anesthesia method: DPC method (intravenous sedation combined with intravenous anesthesia) Medical history: Depression, panic disorder, diabetes, hypertension, reflux esophagitis, angina pectoris, arrhythmia (tachycardia) Surgery / anesthesia history: Cesarean section (2 times: spinal) Oral medications: Equa (DPP-4 inhibitor) morning and evening, Persantin (coronary vasodilator), Mainstay (beta-blocker), Mexile (sodium channel blocker), Fluboxane (SSRI), Nexium (PPI)

[0039] Anesthesia progress Intravenous anesthetic used (1) Dex Loading phase: Administer at a dose of 6 mcg / kg / h (75 ml / h) over 10 minutes, calculated based on ideal body weight (BMI 22, 49.36 kg ≈ 50 kg). For sedated procedures (surgery, suturing): Administer 0.2 mcg / kg / h (4.5 ml / h) until the end of surgery, calculated based on actual body weight (BMI 39.77, 89.3 kg ≈ 90 kg). (2) Pro Sedation-controlled procedure (surgery, suturing): Based on actual body weight (BMI 39.77, 89.3kg ≈ 90kg), the blood concentration is calculated and administered at an effective site concentration of approximately 0.7mcg / ml from the end of the loading phase until the end of the surgery.

[0040] Progression of vital signs Preoperative: Blood pressure 133-126 / 93-58 mmHg, pulse 101-103 bpm, SpO2 96% Intraoperative: Refer to the anesthesia record (Figure 1). The abbreviations shown in Figure 1 and the following figures indicate the following: HR: Pulse rate SYS: Systolic blood pressure DIA: Diastolic blood pressure SpO2: Oxygen saturation As shown in Figure 1, vital signs remained generally stable throughout the loading and sedation-controlled treatment phases.

[0041] <Case 2 MM> Patient: MM Age: 42 Gender: Female Height: 156.9m Weight: 97.9kg BMI: 39.8 Procedure: 876┬8 Tooth extraction (remaining root) Anesthesia method: DPC method (intravenous sedation combined with intravenous anesthesia) Medical history: Asthma, rheumatoid arthritis, hyperuricemia History of surgery / anesthesia: None Oral medications: Montecast, Xyzal, Recetirizine, Relvar, Duphaston

[0042] Anesthesia progress Intravenous anesthetic used (1) DEX Loading phase: Administer at a dose of 6 mcg / kg / h (82 ml / h) over 10 minutes, adjusted to an ideal body weight (BMI 22, 54.158 kg ≈ 55 kg). Procedure under sedation (surgery, suturing): Administer 0.2 mcg / kg / h (4.5 ml / h) until the end of surgery, calculated based on actual body weight (97.9 kg ≈ 100 kg). (2) Pro Procedures performed under sedation (surgery, suturing): Blood concentration is calculated based on actual body weight (97.9 kg ≈ 100 kg). After the loading phase of DEX is complete, administer it at an effective site concentration of approximately 0.4 mcg / ml until the end of the surgery. Surgery duration: 27 minutes (from start to finish) (3) Progress of vital signs Preoperative: Blood pressure 113-104 / 69-54 mmHg, pulse 74-79 bpm, SpO2 98% Intraoperative: Refer to the anesthesia record (Figure 2). As shown in Figure 2, vital signs remained generally stable throughout the loading and sedation-controlled treatment phases.

[0043] <Case 3 KK> Patient: KK Age: 35 Gender: Female Height: 154.1cm Weight: 70kg BMI: 29.5 Procedure: 8. Tooth Extraction Anesthesia method: DPC method (intravenous sedation combined with intravenous anesthesia) Medical history: No special notes. Surgery / anesthesia history: Ovarian cyst surgery (Epi+ whole) Oral medications: None Allergy: Latex allergy

[0044] Anesthesia progress Intravenous anesthetic used (1) DEX Loading phase: Administer at a dose of 6 mcg / kg / h (73 ml / h) over 10 minutes, adjusted to an ideal body weight (BMI 22, 52.2 kg ≈ 52 kg). For sedated procedures (surgery, suturing): Administer 0.5 mcg / kg / h (8.8 ml / h) until the end of surgery, calculated based on actual body weight (70.0 kg). (2) Pro Sedation-controlled procedure (surgery, suturing): Based on actual body weight (70.0 kg), the blood concentration is calculated and administered at an effective site concentration of approximately 0.7-0.8 mcg / ml from the end of the loading phase until the end of the surgery.

[0045] Progression of vital signs Preoperative blood pressure 116-120 / 89-81 mmHg, pulse 60-63 bpm, SpO2 99% Refer to the intraoperative anesthesia record (Figure 3). As shown in Figure 3, vital signs remained generally stable throughout the loading and sedation-controlled treatment phases.

[0046] <Case 4 TT> Patient: TT Age: 48 Gender: Male Height: 164cm Weight: 56kg BMI: 20.8 Procedure: Placement of 6 implants (upper jaw) Anesthesia method: DPC method (intravenous sedation combined with intravenous anesthesia) Medical history: No special notes. Surgery / anesthesia history: No special notes. Oral medications: None Allergies: None

[0047] Anesthesia progress Intravenous anesthetic used (1) DEX Loading process: Convert to predicted weight: 50 + 0.91 (height in cm - 152.4 cm) = 60.556 kg Administer 6 mcg / kg / h (90 ml / h) over 10 minutes. Sedation-controlled procedure (surgery, before suturing): Starting dose was 0.5 mcg / kg / h (6.9 ml / h) based on actual body weight (56 kg ≈ 55 kg), but was increased to 0.4 mcg / kg / h as bradycardia progressed, and administered until implant placement was complete. Stopped before suturing. (2) Pro Sedation-controlled procedure ~ suturing process: Based on actual body weight (56kg), the blood concentration is calculated and administered at an effective site concentration of approximately 0.8mcg / ml from the end of the DEX loading phase until the end of the surgery.

[0048] Progression of vital signs Preoperative blood pressure 140 / 85 mmHg, pulse 60-63 bpm, SpO2 99-100% Refer to the intraoperative anesthesia record (Figure 4). During the procedure, the patient alternated between sleeping and being awake. As shown in Figure 4, vital signs remained generally stable throughout the loading process, the sedation-assisted procedure, and the suturing process.

[0049] <Case 5™> Patient: TM Age: 61 Gender: Female Height: 157cm Weight: 51kg BMI: 20.96 Procedure: Placement of 9 implants (upper jaw) Anesthesia method: DPC method (intravenous sedation combined with intravenous anesthesia) Medical history: No special notes. Surgery / anesthesia history: Left anterior cruciate ligament surgery (Epi) Oral medications: None Allergies: None

[0050] Anesthesia progress Intravenous anesthetic used (1) DEX Loading phase: Administer 6 mcg / kg / h (85 ml / h) over 10 minutes, calculated based on ideal body weight (54.2278 kg). Sedation-controlled procedure (until surgery and suturing): Administer at a rate of 0.5 mcg / kg / h (6.7 ml / h) calculated based on actual body weight (51 ≈ 50 kg) until implant placement is complete. Stop administration before suturing begins. (2) Pro Sedation-controlled procedure ~ suturing process: Based on actual body weight (51kg), the blood concentration was calculated and administered at an effective site concentration of approximately 0.7-0.8mcg / ml from the end of the DEX loading phase until the end of the surgery.

[0051] Progression of vital signs Preoperative blood pressure 130 / 75 mmHg, pulse 80-83 bpm, SpO2 98% Refer to the intraoperative anesthesia record (Figure 5). As shown in Figure 5, vital signs remained generally stable throughout the loading process, the sedation-assisted procedure, and the suturing process.

[0052] <Case 6 TS> Patient: TS Age: 59 Gender: Male Height: 167.3cm Weight: 74.2kg BMI: 26.6 Procedure: 8. Tooth Extraction Anesthesia method: DPC method (intravenous sedation combined with intravenous anesthesia) Medical history: hypertension, dyslipidemia, diabetes, mild hepatic dysfunction. Surgery and Anesthesia History: Around age 6, inguinal hernia surgery (general anesthesia) Oral medications: Amlodipine, Ezetimibe Allergies: Hay fever

[0053] Anesthesia progress Intravenous anesthetic used (1) DEX Loading phase: Administer at a dose of 6 mcg / kg / h (90 ml / h) over 10 minutes, adjusted to an ideal body weight (BMI 22, 61.6 kg ≈ 60 kg). For sedated procedures (surgery, suturing): Administer at a rate of 0.5 mcg / kg / h (9.4 ml / h) - 0.4 mcg / kg / h (7.5 ml / h) until the end of surgery, calculated based on actual body weight (74.2 kg ≈ 75 kg). (2) Pro Sedation-controlled procedure (surgery, suturing): Based on actual body weight (74.2 kg ≈ 75 kg), the blood concentration is calculated and administered at an effective site concentration of approximately 0.7-0.8 mcg / ml from the end of the loading phase until the end of the surgery.

[0054] Progression of vital signs Preoperative blood pressure 127-132 / 73-72 mmHg, pulse 88-91 bpm, SpO2 98% Refer to the intraoperative anesthesia record (Figure 6). findings During the procedure, she dozed off and woke up intermittently, and only woke up when she was told to "breathe through your nose."

[0055] <Case 7 SG> Patient: SG Age: 31 Gender: Female Height: 151.3cm Weight: 44.4kg BMI: 19.4 Procedure: ├8 Tooth extraction Anesthesia method: MP method, midazolam and propofol combination (intravenous sedation combined with intravenous anesthesia) Medical history: No special notes. Surgery / Anesthesia History: March 16, 2022 8. Midazolam and propofol combined sedation (at our hospital) Apparently, she was mostly asleep during the surgery. Oral medications: None Allergies: Itching from latex, melons (watermelon, melon), and fruits (apples, peaches, kiwis, bananas, etc.)

[0056] Anesthesia progress Intravenous anesthetic used (1) Midazolam 3.5 mg (total amount) (2) Pro Maintenance (surgery, suturing): Calculate the blood concentration based on actual body weight (BMI 19.4, 44.4 kg) and administer at an effective site concentration of approximately 1.1-1.2 mcg / ml until the end of surgery. Progression of vital signs Preoperative blood pressure 97-110 / 57-74 mmHg, pulse 57-61 bpm, SpO2 100% Refer to the intraoperative anesthesia record (Figure 7). The patient was in so much pain that they were awake during the procedure to remove their lower wisdom tooth. A drop in blood pressure was observed.

[0057] <Case 8 MN> Patient: MN Age: 22 Gender: Female Height: 160cm Weight: 58kg BMI: 22 Procedure: Extraction of tooth #8 Anesthesia method: MP method, midazolam and propofol combination (intravenous sedation combined with intravenous anesthesia) Medical history: History of HVS during mental stress Surgical / anesthesia history: No special notes (HVS occurred during tooth extraction of tooth ┌8 at a nearby dental clinic 3 years ago). Oral medications: None Allergies: None

[0058] Anesthesia progress Intravenous anesthetic used (1) Midazolam 4.5 mg (total amount) (2) Pro Maintenance (surgery, suturing): Calculate the blood concentration based on actual body weight (BMI 22, 58 kg) and administer at an effective site concentration of approximately 1.4-1.5 mcg / ml until the end of surgery.

[0059] Progression of vital signs Preoperative blood pressure 112-116 / 65-86 mmHg, pulse 98-108 bpm, SpO2 100% Refer to the intraoperative anesthesia record (Figure 8). The moment the surgeon touched the patient's oral cavity, the patient exhibited a pained expression and developed HPV (hypoxic pulmonary vasoconstriction). After waiting for the hyperventilation to subside, the procedure was resumed, but the patient again exhibited a pained expression and HPV the moment the surgeon touched the oral cavity. Due to the frequent occurrence of this symptom, it was determined that safe IVS (intravenous vasoconstriction) was difficult, and the procedure was discontinued. This is likely a paradoxical reaction.

[0060] <Case 9-1 AI> (Cases 9-1 to 9-3 are the same patient) Patient: AI Age: 36 Gender: Female Height: 163cm Weight: 94.0kg BMI: 35.25 Procedure: Tooth extraction Anesthesia method: MP method, midazolam and propofol combination (intravenous sedation combined with intravenous anesthesia) Medical history: History of HVS during mental stress Surgical / anesthesia history: No special notes (HVS occurred at a nearby dental clinic). Oral medications: None Allergies: None

[0061] Anesthesia progress Intravenous anesthetic used (1) Midazolam 3 mg (total amount) (2) Pro Maintenance (surgery, suturing): Calculate the blood concentration based on actual body weight (94.0 kg) and administer at an effective site concentration of approximately 0.6-0.9 mcg / ml until the end of surgery.

[0062] Progression of vital signs Preoperative blood pressure 131-124 / 73-79 mmHg, pulse 98 bpm, SpO2 100% Refer to the intraoperative anesthesia record (Figure 9-1). Hypoventilation occurred, and SpO2 dropped to around 85% during the surgery.

[0063] <Case 9-2 AI> (Cases 9-1 to 9-3 are the same patient) Patient: AI Age: 36 Gender: Female Height: 163cm Weight: 94.0kg BMI: 35.25 Procedure: Tooth extraction Anesthesia method: MP method, midazolam and propofol combination (intravenous sedation combined with intravenous anesthesia) Medical history: History of HVS during mental stress Surgical / anesthesia history: No special notes (HVS occurred at a nearby dental clinic). Oral medications: None Allergies: None

[0064] Anesthesia progress Intravenous anesthetic used (1) Midazolam 2.5 mg (total amount) (2) Pro Maintenance (surgery, suturing): Calculate the blood concentration based on actual body weight (94.0 kg) and administer at an effective site concentration of approximately 0.4-0.56 mcg / ml until the end of surgery.

[0065] Progression of vital signs Preoperative blood pressure 131-124 / 73-79 mmHg, pulse 98 bpm, SpO2 100% Refer to the intraoperative anesthesia record (Figure 9-2). The patient experienced frequent hypoventilation, and SpO2 levels dropped to around 85% during surgery, requiring oxygen administration midway through the procedure.

[0066] <Case 9-3 AI> (Cases 1-3 in Case 9 are the same patient) Patient: AI Age: 36 Gender: Female Height: 163cm Weight: 89.9kg BMI: 33.75 Procedure: Tooth extraction Anesthesia method: DPC method (intravenous sedation combined with intravenous anesthesia) Medical history: History of HVS during mental stress Surgical / anesthesia history: No special notes (HVS occurred at a nearby dental clinic). Oral medications: None Allergies: None

[0067] Anesthesia progress Intravenous anesthetic used (1) DEX Loading phase: Administer at a dose of 6 mcg / kg / h (90 ml / h) over 10 minutes, adjusted to an ideal body weight (BMI 22, 58.7 kg ≈ 60 kg). For sedated procedures (surgery, suturing): Administer 0.5 mcg / kg / h (11.3 ml / h) until the end of surgery, calculated based on actual body weight (89.9 kg ≈ 90 kg). (2) Pro Sedation-controlled procedure (surgery, suturing): Based on actual body weight (89.9kg ≈ 90kg), the blood concentration is calculated and administered at an effective site concentration of approximately 0.5-0.6 mcg / ml from the end of the loading phase until the end of the surgery.

[0068] Progression of vital signs Preoperative blood pressure 131-124 / 73-79 mmHg, pulse 98 bpm, SpO2 100% Refer to the intraoperative anesthesia record (Figure 9-3).

[0069] During the procedure, the patient dozed off and woke up intermittently, only noticing and waking up when told to "breathe through your nose." The SpO2 level only dropped to a minimum of 96%, and when there was a tendency towards hypoventilation, simply encouraging breathing through verbal prompting was enough to improve the condition. There was also minimal body movement.

[0070] <Case 10-1 HI> (Cases 10-1 and 10-2 are the same patient) Patient: AI Age: 22 Gender: Female Height: 164.3cm Weight: 43.9kg BMI: 16.3 Procedure: 8. Tooth Extraction Anesthesia method: MP method, midazolam and propofol combination (intravenous sedation combined with intravenous anesthesia) Medical history: History of HVS during mental stress Surgery / Anesthesia History: Endometrial stripping under general anesthesia (No special notes) Oral medications: None Allergies: None

[0071] Anesthesia progress Intravenous anesthetic used (1) Midazolam 2 mg (total amount) (2) Pro Maintenance: Administer the drug at an effective site concentration of approximately 1.2 mcg / ml, calculated based on actual body weight (43.9 kg), until the end of surgery.

[0072] Progression of vital signs Preoperative blood pressure 113-95 / 54-47 mmHg, pulse 83-88 bpm, SpO2 100-99% Refer to the intraoperative anesthesia record (Figure 10-1). The turbine water injection caused frequent coughing and large body movements.

[0073] <Case 10-2 HI> (Case 10-1 and 10-2 are the same case) Patient: AI Age: 22 Gender: Female Height: 164.3cm Weight: 43.9kg BMI: 16.3 Procedure: 8. Tooth Extraction Anesthesia method: DPC method (intravenous sedation combined with intravenous anesthesia) Medical history: History of HVS during mental stress Surgery / Anesthesia History: Endometrial stripping under general anesthesia (No special notes) Medications: None Allergies: None

[0074] Anesthesia progress Intravenous anesthetic used (1) DEX Initial dose: 6 mcg / kg / h (90 ml / h) administered over 10 minutes, calculated based on ideal body weight (BMI 22, 59.4 kg ≈ 60 kg). Maintenance: Administer at a rate of 0.5 mcg / kg / h (5.65 ml / h) until the end of surgery, calculated based on actual body weight (43.9 kg ≈ 45 kg). (2) Pro Maintenance: Based on actual body weight (44.9 kg ≈ 45 kg), the blood concentration is calculated and administered at an effective site concentration of approximately 0.5-0.6 mcg / ml from the end of DEX loading until the end of surgery.

[0075] Progression of vital signs Preoperative blood pressure 131-124 / 73-79 mmHg, pulse 98 bpm, SpO2 100% Refer to the intraoperative anesthesia record (Figure 10-2).

[0076] During the previous procedure, the patient frequently choked when the turbine water was injected, but this time there was almost no coughing. Also, there was no movement at all. The patient said they don't remember anything about the procedure. My impression after the procedure was that the time it took for the effects of DEX to wear off was a little longer than usual.

[0077] <Case 11 HH> Patient: HH Age: 59 Gender: Female Height: 164cm Weight: 50.5kg BMI: 18.7 Procedure: Placement of 8 implants (lower jaw) Anesthesia method: DPC method (intravenous sedation combined with intravenous anesthesia) Medical history: No special notes Surgery / anesthesia history: No special notes. Oral medications: None Allergies: None

[0078] Anesthesia progress Intravenous anesthetic used (1) DEX Loading phase: Administer 6 mcg / kg / h (83.5 ml / h) over 10 minutes, calculated based on the estimated body weight (56.056 kg ≈ 55 kg). For sedated procedures (surgery, suturing): Administer 0.4-0.3 mcg / kg / h (5-3.8 ml / h) until the end of surgery, calculated based on actual body weight (50.5 kg ≈ 50 kg). (2) Pro For sedated procedures (surgery, suturing): Blood concentration is calculated based on actual body weight (50.5 kg ≈ 50 kg), and DEX is administered at an effective site concentration of approximately 0.45-0.5 mcg / ml from the end of the loading phase until the end of the surgery.

[0079] Progression of vital signs Preoperative blood pressure 128 / 75 mmHg, pulse 73 bpm, SpO2 100% Refer to the intraoperative anesthesia record (Figure 11). During the procedure, the patient was reportedly drowsy, alternating between sleeping and waking. Opening and closing the mouth during the procedure appeared to be without any problems.

[0080] <Case 12 KN> Patient: KN Age: 54 Gender: Female Height: 143.5cm Weight: 70.4kg BMI: 34.19 Procedure: 87┐Tooth Extraction Anesthesia method: DPC method (intravenous sedation combined with intravenous anesthesia) Medical history: No special notes Surgery / anesthesia history: No special notes. Oral medications: None Allergies: None

[0081] Anesthesia progress Intravenous anesthetic used (1) DEX Loading phase: Administer at a rate of 6 mcg / kg / h (67.5 ml / h) over 10 minutes, calculated based on the expected body weight (45.3 kg ≈ 45 kg). Sedation-controlled procedure (tooth extraction): Based on actual body weight (BMI 34.19, 70.4kg ≈ 70kg), administer 0.5mcg / kg / h (8.8 ml / h) until tooth extraction is complete. (2) Pro The blood concentration was calculated for a sedated procedure (tooth extraction) (BMI 34.19, 70.4kg ≈ 70kg), and the effective site concentration of DEX was administered at approximately 0.5 mcg / ml from the end of the loading phase until the end of the surgery.

[0082] Progression of vital signs Preoperative blood pressure 140 / 80 mmHg, pulse 58-59 bpm, SpO2 100% Refer to the intraoperative anesthesia record (using high-flow nasal anesthetic) (Figure 12). The patient said they don't remember anything during the procedure. They seemed to be able to open and close their mouth without any problems during the procedure. There was very little body movement.

[0083] <Case 13 SS> Patient: SS Age: 56 Gender: Female Height: 156.1cm Weight: 51.3kg BMI: 21.1 Procedure: 1┘C Dental Procedure Anesthesia method: DPC method (intravenous sedation combined with intravenous anesthesia) Medical history: Dental phobia, Meniere's disease Surgery / anesthesia history: Cervical spondylosis surgery (C2: limited cervical range of motion) Oral medications: None Allergies: Shellfish, melon, peach, alcohol allergy

[0084] Anesthesia progress Intravenous anesthetic used (1) DEX Loading phase: Administer at a rate of 6 mcg / kg / h (79.5 ml / h) over 10 minutes, calculated based on ideal body weight (53.6 kg ≈ 53 kg). Procedure under sedation: Based on actual body weight (BMI 21.1, 51.3kg ≈ 51kg), administer 0.5mcg / kg / h (6.42 ml / h) until tooth extraction is complete.

[0085] (2) Pro Procedure under sedation: Blood concentration is calculated based on actual body weight (BMI 21.1, 51.3kg ≈ 51kg). After the loading phase of DEX is complete, administer it at an effective site concentration of approximately 0.5-0.8 mcg / ml until the end of surgery.

[0086] Progression of vital signs Preoperative blood pressure 141 / 72 mmHg, pulse 69-70 bpm, SpO2 100% Refer to the intraoperative anesthesia record (Figure 13). The patient said they don't remember anything during the procedure. They seemed to be able to open and close their mouth without any problems during the procedure. There was very little body movement. Choking occurred due to insufficient suction from the oral vacuum.

[0087] <Case 14 SF> Patient: SF Age: 44 Gender: Female Height: 157.6cm Weight: 51.4kg BMI: 20.7 Procedure: 32┬3 Tooth Extraction Anesthesia method: DPC method (intravenous sedation combined with intravenous anesthesia) Medical history: Insufficient response to dental local anesthesia Surgical and Anesthesia History: Postoperative nausea and vomiting (PONV) after total hysterectomy under general anesthesia for cervical cancer. Oral medication: Estrana patch Allergies: None

[0088] Anesthesia progress Intravenous anesthetic used (1) DEX Loading phase: Administer at a rate of 6 mcg / kg / h (82.5 ml / h) over 10 minutes, calculated based on ideal body weight (54.6 kg ≈ 55 kg). Sedation-supported procedure (tooth extraction): Based on actual body weight (BMI 20.7, 51.4 kg ≈ 50 kg), administration began at 0.5 mcg / kg / h (6.3 ml / h) after a 10-minute loading period. However, when the patient switched to the maintenance dose, a drop in systolic blood pressure to the 70 mmHg range was observed, so administration was discontinued.

[0089] (2) Pro Procedure under sedation: Blood concentration is calculated based on actual body weight (BMI 20.7, 51.4kg ≈ 50kg). After the loading phase of DEX was completed, the drug was administered at an effective site concentration of approximately 0.5 mcg / ml for about 40 minutes, but administration was discontinued due to persistent hypotension.

[0090] Progression of vital signs Preoperative blood pressure 141 / 72 mmHg, pulse 69-70 bpm, SpO2 100% Refer to the intraoperative anesthesia record (Figure 14).

[0091] A drop in blood pressure was observed immediately after the completion of DEX loading. Ephedrine-induced blood pressure elevation was ineffective, so phenylephrine administration was used to raise blood pressure. During the postoperative recovery period, approximately 300 ml of colloid solution (Volube) was administered intravenously, and blood pressure was elevated twice with Ephedrine. The drop in blood pressure resolved approximately two hours after the completion of the procedure (DEX half-life).

[0092] The patient said they don't remember anything during the procedure. They seemed to be able to open and close their mouth without any problems during the procedure. There was very little body movement. Choking occurred due to insufficient suction from the oral vacuum.

[0093] The following was considered based on this case. Causes of blood pressure drop immediately after loading: (1) If the BMI is less than 21, it is considered easier to prevent a drop in blood pressure due to an overdose of DEX by using actual body weight rather than ideal body weight. (2) The package insert for Estrana Tape lists elevated blood pressure as a side effect, and this may be the side effect in this case.

[0094] Future measures If the BMI is less than 21, the DEX loading amount will be calculated based on actual body weight.

[0095] <Case 15 KM> Patient: KM Age: 62 Gender: Female Height: 153.8cm Weight: 53.8kg BMI: 22.7 Procedure: 1┘C Dental Procedure Anesthesia method: DPC method (intravenous sedation combined with intravenous anesthesia) Past medical history: hyperthyroidism Surgery / anesthesia history: Appendicitis (spinal subarachnoid anesthesia: no adverse reaction) Oral medications: None Allergies: None

[0096] Anesthesia progress Intravenous anesthetic used (1) DEX Loading phase: Administer 6 mcg / kg / h (78 ml / h) over 10 minutes, calculated based on ideal body weight (52 kg). Procedure under sedation: Based on actual body weight (BMI 22, 53.8kg ≈ 54kg), administer 0.5mcg / kg / h (6.42 ml / h) until tooth extraction is complete. (2) Pro Procedure under sedation: Blood concentration is calculated based on actual body weight (BMI 22.7, 53.8kg ≈ 54kg). After the loading phase of DEX is complete, administer it at an effective site concentration of approximately 0.35-0.4 mcg / ml until the end of surgery.

[0097] Progression of vital signs Preoperative blood pressure 141 / 72 mmHg, pulse 61-70 bpm, SpO2 100% Refer to the intraoperative anesthesia record (Figure 15). The patient said they don't remember anything during the procedure. They seemed to have no problem opening and closing their mouth during the procedure. There was very little body movement. They were snoring.

[0098] <Cases 16-1 and 16-2 MM> Patient: MM Age: 49 Gender: Male Height: 169.1cm Weight: 68.3kg BMI: 23.9 Medical history: Migraine (currently being treated with oral medication) Surgical and Anesthesia History: Lumbar disc herniation surgery, spinal subarachnoid anesthesia (no special notes) Oral medications: Inderal, Selenica, Rivotril Allergies: None

[0099] Case 16-1 (December 18, 2023) Procedure: Implant placement

[0100] Anesthesia method: MP method, midazolam and propofol combination (intravenous sedation combined with intravenous anesthesia) Anesthesia progress Intravenous anesthetic used (1) Midazolam 2.25 mg (total amount) (2) Pro Procedure under sedation: The blood concentration is calculated based on actual body weight, and the drug is administered at an effective site concentration of approximately 0.75 mcg / ml until the end of the surgery.

[0101] Progression of vital signs Preoperative blood pressure 111-98 / 69-73 mmHg, pulse 57-73 bpm, SpO2 100-99% Refer to the intraoperative anesthesia record (Figure 16-1). The turbine water injection caused frequent coughing and large body movements.

[0102] Case 16-2 (June 27, 2024) Anesthesia progress Intravenous anesthetic used (1) Midazolam 2.25 mg (total amount) (2) Pro Procedure under sedation: The blood concentration is calculated based on actual body weight, and the drug is administered at an effective site concentration of approximately 0.8 mcg / ml until the end of the surgery.

[0103] Progression of vital signs Preoperative blood pressure 114-97 / 69-73 mmHg, pulse 52-78 bpm, SpO2 100-97% Refer to the intraoperative anesthesia record (Figure 16-2). The turbine water injection caused frequent coughing and large body movements.

[0104] <Case 17 DU> Patient: DU Age: 52 Gender: Male Height: 166cm Weight: 66.7kg BMI: 24.2 Procedure: ┌8 Tooth extraction Anesthesia method: MP method, midazolam and propofol combination (intravenous sedation combined with intravenous anesthesia) Medical history: dizziness, inguinal hernia, childhood asthma Surgical and anesthesia history: Inguinal hernia surgery (general anesthesia: nl) Oral medication: Tacrolimus Cefcapene pivoxil tablets Rebamipide Bepotastine besilate tablets Adephos Kowa Allergies: Shrimp, crab, house dust

[0105] Anesthesia progress Intravenous anesthetic used (1) Midazolam 2.5 mg (total amount) (2) Pro Procedure under sedation: The blood concentration is calculated based on actual body weight, and the drug is administered at an effective site concentration of approximately 0.8 mcg / ml until the end of the surgery.

[0106] Progression of vital signs Preoperative blood pressure 134-100 / 77-67 mmHg, pulse 75-62 bpm, SpO2 100-97% Refer to the intraoperative anesthesia record (Figure 17). The turbine water injection caused frequent coughing and large body movements.

[0107] Summary Of the cases, those treated with the DPC method are cases 1-6, 9-3, 10-2, 11, and 12-15, while those treated with the MP method (intravenous sedation combined with intravenous anesthesia) are cases 7, 8, 9-1, 9-2, 10-1, 16-1, 16-2, and 17.

[0108] In cases where midazolam and propofol were used in combination, patients experienced severe pain, remained awake with weak amnesic effects (Case 7), displayed expressions of distress and developed HPV, forcing the surgery to be interrupted (Case 8), and experienced intraoperative hypoventilation (Cases 9-1, 9-2) and choking (Case 10-1), indicating that sufficient intravenous sedation could not be achieved.

[0109] Furthermore, in cases 4 and 5, decusmedetomidine and propofol were administered in combination until the completion of the implant placement procedure, and decusmedetomidine administration was stopped at the start of the suturing process. Compared to cases where decusmedetomidine administration was not stopped at the start of suturing, the time until the patients were able to walk independently and go home was shorter, and earlier recovery was achieved.

[0110] In cases where intravenous sedation combined with dexmedetomidine and propofol (DPC method) was employed (Cases 1-6, 9-3, 10-2, and 11-15), intraoperative vital signs were relatively stable, and the following effects were confirmed. • They awaken when called by name or stimulated. • Less respiratory depression. • Awareness of comfortable sleep. • Amnesia effect.

[0111] Table 1 summarizes the evaluation scores for choking and body movement in cases using both the DPC method and the MP method, based on the criteria shown. Furthermore, the lowest values ​​recorded in the anesthesia records for heart rate, systolic blood pressure, and oxygen saturation in each case were compared. Statistical analysis was performed using the Wilcoxon-Mann-Whitney signed-rank test, and the results are shown in Figures 18-22.

[0112] Significant differences were observed between the DPC method and the MP method for choking, body movement, and systolic blood pressure, confirming that the DPC method was superior. On the other hand, there were no significant differences between the two groups for heart rate and oxygen saturation.

[0113] Furthermore, atropine was administered if severe bradycardia occurred or if bradycardia worsened, and vasopressors were administered if blood pressure dropped too low during surgery. There was no difference in the necessity of administering atropine and vasopressors between the DPC method and the MP method.

Claims

1. The present invention provides a pharmaceutical product used in combination with propofol in a method of inducing sedation in a human subject during dental treatment or oral surgery, wherein the pharmaceutical product contains dexmedetomidine, and the method of inducing sedation in the subject includes the following: (1-1) For patients with a BMI of 22 or higher, a loading procedure is performed before the start of the procedure, in which 3 to 6 μg / kg / h of dexmedetomidine is administered intravenously for approximately 10 minutes based on ideal body weight. (1-2) If the BMI is less than 22, a loading process is performed before the start of the procedure, in which 3 to 6 μg / kg / h of dexmedetomidine based on actual body weight is administered intravenously for about 10 minutes, and (2) After the loading process, sedation is maintained by intravenously administering dexmedetomidine at a rate of 0.2-0.5 μg / kg / h based on actual body weight and propofol so that the blood concentration is 0.4-0.8 μg / ml based on actual body weight, and the procedure is performed under the sedated state.

2. The pharmaceutical product according to claim 1, wherein dental treatment or oral surgery is selected from tooth extraction, bone regeneration induction, exostodectomy, removal of foreign bodies in the jawbone (so-called pin removal: removal of screws, etc.), anchor bolt placement, necrotic bone removal, partial alveolar bone resection, hematoma resection, tongue tumor resection (including leukoplakia and lichen planus), buccal mucosal tumor, removal of foreign bodies in the maxillary sinus, apicoectomy, alveolar bone shaping, dental implant placement, sedation during wound dressing change and disinfection, oral or nasal tracheal intubation, and so-called dental treatment.

3. The pharmaceutical product according to claim 1, wherein the method for inducing sedation in the subject further includes the following steps: (3) A procedure in which the administration of dexmedetomidine is stopped at the start of the suturing process after the procedure, and the suturing process is performed under sedation by intravenous administration of propofol to a blood concentration of 0.4-0.8 μg / ml based on actual body weight.

4. The pharmaceutical product according to claim 2, wherein the oral surgery is selected from tooth extraction, apicoectomy, alveolar bone shaping, and dental implant placement.

5. The pharmaceutical product according to claim 3, wherein the oral surgery is a dental implant placement surgery.

6. The pharmaceutical product according to claim 2, wherein the oral surgery procedure is tooth extraction.

7. The pharmaceutical product according to any one of claims 1 to 6, wherein the human subject is an obese person with a BMI of 30 or higher.

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