Clinical trial NCT06026566: Compatible Effect of Remimazolam Besylate Combined With Afentanil for ATI
Official title: Compatible Dose Study and Effect Observation of Remimazolam Besylate Combined With Afentanil for Awake Endotracheal Intubation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Remimazolam
Awake Endotracheal Intubation
Keywords: Remimazolam
Awake Endotracheal Intubation
Lead sponsor: Tongji Hospital
Sponsor class: OTHER
First posted: 2023-09-07
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: crisscross
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

The purpose of this study is to study the pharmacokinetics between remimazolam besylate and alfentanil hydrochloride by response surface analysis, to determine the standard drug concentration under spontaneous breathing, and to observe the clinical effect of awake tracheal intubation under this concentration dose, to explore the best compatible dose range of the two drugs, in order to provide a reference for clinical application in patients with difficult airway.

Eligibility criteria: Inclusion Criteria:

1. no predictable difficult airway, Mallampati grade Ⅰ-II;
2. deviation from ideal body weight ≤25%;

   \[Ideal weight (kg) = height (cm) -100 (male) or 105 (female)\]
3. American Society of Anesthesiologists grade Ⅰ-II;
4. Informed consent: voluntarily participate in the trial and sign the informed consent.

Exclusion Criteria:

1. 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;
2. Relative contraindications: patients with respiratory diseases, allergy to local anesthetics, airway bleeding, and non-cooperation;
3. patients known to be allergic to remimazolam besylate or benzodiazepines;
4. patients with known allergy to alfentanil or opioids;
5. body weight exceeding ±25% of ideal body weight;
6. patients with coagulation dysfunction, endocrine diseases or other hemodynamic conditions;
7. patients with a history of drug or alcohol dependence;
8. Subjects who were deemed unsuitable for the study by the investigators.

Primary outcomes:
measure: Respiratory Rate
timeFrame: During surgery
measure: Tidal volume
timeFrame: During surgery
measure: Deep breathing
timeFrame: During surgery
measure: Airway obstruction
timeFrame: During surgery
measure: Oxygen saturation decreased
timeFrame: During surgery
Secondary outcomes:
measure: Airway status
timeFrame: During surgery
measure: Intubation response
timeFrame: During surgery
measure: RASS score
timeFrame: During surgery
measure: Hemodynamic assessments
timeFrame: During surgery
measure: The satisfaction of patients and anesthesiologists
timeFrame: Up to 2 hours after surgery
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College, Huazhong Science and Technology University
state: Hubei
Study officials:
affiliation: Tongji Hospital
name: Qiaoqiao Xu
role: PRINCIPAL_INVESTIGATOR
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