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临床试验/NCT06026566
NCT06026566招募中不适用

Compatible Dose Study and Effect Observation of Remimazolam Besylate Combined With Afentanil for Awake Endotracheal Intubation

Tongji Hospital1 个研究点 分布在 1 个国家目标入组 180 人开始时间: 2023年4月1日最近更新:
适应症
干预措施
相关药物

试验速览

阶段
不适用
状态
招募中
入组人数
180
试验地点
1
主要终点
Respiratory Rate

研究概览

简要总结

  1. To study the pharmacokinetics between remimazolam besylate and alfentanil;
  2. To determine the optimal dosage of the two drugs in awake endotracheal intubation;
  3. To provide clinical guidance for awake endotracheal intubation.

详细描述

Tracheal intubation is the most effective and reliable method to establish artificial airway, which provides the best conditions for relieving airway obstruction, ensuring airway patency, removing respiratory secretions, preventing aspiration, assisting or controlling breathing, etc. Difficult airway management strategies must be adopted when patients are predicted to have difficulties in mask ventilation, supraglottic airway device (SAD) placement, or endotracheal intubation and front-of-neck airway (FONA) establishment. Awake tracheal intubation (ATI) is one of the important methods.

ATI refers to tracheal intubation while the patient is awake and breathing spontaneously, most commonly by flexible bronchoscopy (FB) or video laryngoscopy (VL), which allows for airway control prior to induction of general anesthesia. Thus, the potential risks and consequences of difficulty in establishing the airway after anesthesia induction are avoided. The safety of ATI is reflected in the guarantee of spontaneous breathing and intrinsic airway tension of patients before tracheal tube insertion. The failure rate of ATI is only 1-2%, and it rarely requires airway first aid or causes patient death.

ATI is currently the safest technique for dealing with difficult airways, but it accounts for only 0.2% of all tracheal intubation types in the UK. The reason is that ATI operators may be under great physical, mental, and psychological stress, which may lead to poor performance and increase the risk of complications, including failure. In addition, mechanical stimulation of the airway in the awake state can cause coughing, nausea, restlessness and other reactions to tracheal intubation, resulting in adverse consequences. Therefore, before the effective implementation of ATI, anesthesiologists often choose to combine small doses of analgesic and sedative drugs to achieve the minimum degree of sedation effect, so as to reduce the anxiety and discomfort of patients and improve the tolerance of patients.

Studies have shown that drugs such as fentanyl, remifentanil, midazolam, propofol and dexmedetomidine can be used to assist ATI to improve patient satisfaction and reduce the risk of excessive sedation and airway obstruction. However, these drugs have different degrees of cardiovascular or respiratory adverse reactions, especially when used in large doses, which increases the risk of hypoxemia, hypotension or bradycardia. ATI guidelines suggest that excessive sedation is very dangerous for some patients, and it is recommended to use it with caution, and a minimum degree of reversible sedation is preferred. Therefore, how to ensure good sedation and analgesia and maintain normal spontaneous breathing is worthy of further study.

Remimazolam besylate is a new type of benzodiazepine, which is an ultra-short-acting sedative/anesthetic drug. The mechanism is that by binding to benzodiazepine receptors, it specifically acts on GABAA receptors, enhances GABAA receptor activity, and selectively promotes extracellular chloride ions into cells, leading to hyperpolarization of cell membrane resting potential and decreased excitability, thus inhibiting neuronal electrical activity and producing sedative effect. And this effect can be specifically antagonized by flumazenil. As an important member of opioid receptor agonist, 30s of alfentanil exerts its drug effect, and its safety is far better than that of morphine. Alfentanil does not cause severe respiratory depression in the therapeutic dose range, and can reduce the use of sedative drugs when used in combination. In gastrointestinal endoscopy, hysteroscopy, fiberoptic bronchoscopy and other procedures with spontaneous breathing, alfentanil alone or in combination with benzodiazepines shows mild respiratory depression and high safety.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Crossover
主要目的
Treatment
盲法
Single (Participant)

入排标准

年龄范围
18 Years 至 65 Years(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • no predictable difficult airway, Mallampati grade Ⅰ-II;
  • deviation from ideal body weight ≤25%;
  • [Ideal weight (kg) = height (cm) -100 (male) or 105 (female)]
  • American Society of Anesthesiologists grade Ⅰ-II;
  • Informed consent: voluntarily participate in the trial and sign the informed consent.

排除标准

  • patients with head and neck lesions (including malignant tumors, previous surgery or radiotherapy), limited mouth opening, limited neck extension, obstructive sleep apnea, morbid obesity, and progressive airway injury;
  • Relative contraindications: patients with respiratory diseases, allergy to local anesthetics, airway bleeding, and non-cooperation;
  • patients known to be allergic to remimazolam besylate or benzodiazepines;
  • patients with known allergy to alfentanil or opioids;
  • body weight exceeding ±25% of ideal body weight;
  • patients with coagulation dysfunction, endocrine diseases or other hemodynamic conditions;
  • patients with a history of drug or alcohol dependence;
  • Subjects who were deemed unsuitable for the study by the investigators.

研究组 & 干预措施

Dos of R 0.1

Experimental

The dosage of Remimazolam Besylate is 0.1 mg/kg

干预措施: Dos of Afentanil 50 (Drug)

Dos of R 0.1

Experimental

The dosage of Remimazolam Besylate is 0.1 mg/kg

干预措施: Dos of Afentanil 60 (Drug)

Dos of R 0.1

Experimental

The dosage of Remimazolam Besylate is 0.1 mg/kg

干预措施: Dos of Afentanil 70 (Drug)

Dos of R 0.1

Experimental

The dosage of Remimazolam Besylate is 0.1 mg/kg

干预措施: Dos of Afentanil 80 (Drug)

Dos of R 0.1

Experimental

The dosage of Remimazolam Besylate is 0.1 mg/kg

干预措施: Dos of Afentanil 90 (Drug)

Dos of R 0.1

Experimental

The dosage of Remimazolam Besylate is 0.1 mg/kg

干预措施: Dos of Afentanil 100 (Drug)

Dos of R 0.15

Experimental

The dosage of Remimazolam Besylate is 0.15 mg/kg

干预措施: Dos of Afentanil 40 (Drug)

Dos of R 0.15

Experimental

The dosage of Remimazolam Besylate is 0.15 mg/kg

干预措施: Dos of Afentanil 50 (Drug)

Dos of R 0.15

Experimental

The dosage of Remimazolam Besylate is 0.15 mg/kg

干预措施: Dos of Afentanil 60 (Drug)

Dos of R 0.15

Experimental

The dosage of Remimazolam Besylate is 0.15 mg/kg

干预措施: Dos of Afentanil 70 (Drug)

Dos of R 0.15

Experimental

The dosage of Remimazolam Besylate is 0.15 mg/kg

干预措施: Dos of Afentanil 80 (Drug)

Dos of R 0.15

Experimental

The dosage of Remimazolam Besylate is 0.15 mg/kg

干预措施: Dos of Afentanil 90 (Drug)

Dos of R 0.2

Experimental

The dosage of Remimazolam Besylate is 0.2 mg/kg

干预措施: Dos of Afentanil 30 (Drug)

Dos of R 0.2

Experimental

The dosage of Remimazolam Besylate is 0.2 mg/kg

干预措施: Dos of Afentanil 40 (Drug)

Dos of R 0.2

Experimental

The dosage of Remimazolam Besylate is 0.2 mg/kg

干预措施: Dos of Afentanil 50 (Drug)

Dos of R 0.2

Experimental

The dosage of Remimazolam Besylate is 0.2 mg/kg

干预措施: Dos of Afentanil 80 (Drug)

Dos of R 0.2

Experimental

The dosage of Remimazolam Besylate is 0.2 mg/kg

干预措施: Dos of Afentanil 60 (Drug)

Dos of R 0.2

Experimental

The dosage of Remimazolam Besylate is 0.2 mg/kg

干预措施: Dos of Afentanil 70 (Drug)

Dos of R 0.25

Experimental

The dosage of Remimazolam Besylate is 0.25 mg/kg

干预措施: Dos of Afentanil 30 (Drug)

Dos of R 0.25

Experimental

The dosage of Remimazolam Besylate is 0.25 mg/kg

干预措施: Dos of Afentanil 40 (Drug)

Dos of R 0.25

Experimental

The dosage of Remimazolam Besylate is 0.25 mg/kg

干预措施: Dos of Afentanil 50 (Drug)

Dos of R 0.25

Experimental

The dosage of Remimazolam Besylate is 0.25 mg/kg

干预措施: Dos of Afentanil 60 (Drug)

Dos of R 0.25

Experimental

The dosage of Remimazolam Besylate is 0.25 mg/kg

干预措施: Dos of Afentanil 80 (Drug)

Dos of R 0.25

Experimental

The dosage of Remimazolam Besylate is 0.25 mg/kg

干预措施: Dos of Afentanil 70 (Drug)

Dos of R 0.3

Experimental

The dosage of Remimazolam Besylate is 0.3 mg/kg

干预措施: Dos of Afentanil 20 (Drug)

Dos of R 0.3

Experimental

The dosage of Remimazolam Besylate is 0.3 mg/kg

干预措施: Dos of Afentanil 30 (Drug)

Dos of R 0.3

Experimental

The dosage of Remimazolam Besylate is 0.3 mg/kg

干预措施: Dos of Afentanil 40 (Drug)

Dos of R 0.3

Experimental

The dosage of Remimazolam Besylate is 0.3 mg/kg

干预措施: Dos of Afentanil 50 (Drug)

Dos of R 0.3

Experimental

The dosage of Remimazolam Besylate is 0.3 mg/kg

干预措施: Dos of Afentanil 60 (Drug)

Dos of R 0.3

Experimental

The dosage of Remimazolam Besylate is 0.3 mg/kg

干预措施: Dos of Afentanil 70 (Drug)

Dos of R 0.35

Experimental

The dosage of Remimazolam Besylate is 0.25 mg/kg

干预措施: Dos of Afentanil 20 (Drug)

Dos of R 0.35

Experimental

The dosage of Remimazolam Besylate is 0.25 mg/kg

干预措施: Dos of Afentanil 30 (Drug)

Dos of R 0.35

Experimental

The dosage of Remimazolam Besylate is 0.25 mg/kg

干预措施: Dos of Afentanil 40 (Drug)

Dos of R 0.35

Experimental

The dosage of Remimazolam Besylate is 0.25 mg/kg

干预措施: Dos of Afentanil 50 (Drug)

Dos of R 0.35

Experimental

The dosage of Remimazolam Besylate is 0.25 mg/kg

干预措施: Dos of Afentanil 60 (Drug)

Dos of R 0.35

Experimental

The dosage of Remimazolam Besylate is 0.25 mg/kg

干预措施: Dos of Afentanil 70 (Drug)

结局指标

主要结局

Respiratory Rate

时间窗: During surgery

RR≤8bpm means respiratory rate decreased after the use of Remimazolam Besylate and Afentanil.

Tidal volume

时间窗: During surgery

Vt≤5ml/kg means tidal volume decreased after the use of Remimazolam Besylate and Afentanil.

Deep breathing

时间窗: During surgery

Breathing hard and deep, and then PetCO2≥55mmHg mean deep breathing after the use of Remimazolam Besylate and Afentanil.

Airway obstruction

时间窗: During surgery

Difficulty in ventilation means airway obstruction after the use of Remimazolam Besylate and Afentanil.

Oxygen saturation decreased

时间窗: During surgery

SpO2≤94% means oxyfen saturation decreased after the use of Remimazolam Besylate and Afentanil.

次要结局

  • Airway status(During surgery)
  • Intubation response(During surgery)
  • RASS score(During surgery)
  • Hemodynamic assessments(During surgery)
  • The satisfaction of patients and anesthesiologists(Up to 2 hours after surgery)

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

Qiaoqiao Xu

Associate professor and deputy chief physician

Tongji Hospital

研究点 (1)

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