Impact of opioids on heart rate during rapid sequence intubation : Double-blind randomized controlled study (CANDY-CRASH).

The primary objective of this study is to **assess the impact of opioids on heart rate** during laryngoscopy at the time of intubation in rapid sequence. This is clinically relevant as it addresses the cardiovascular stability of patients undergoing rapid sequence induction, particularly those with a full stomach, which is a critical concern in anesthesia management.

Secondary objectives include:

• Improving intubation conditions, which is essential for patient safety and procedural success.
• Assessing side effects according to the opioids used, which is important for optimizing drug selection and minimizing adverse effects.
• Evaluating significant variation in hemodynamic responses, which can influence perioperative management and patient outcomes.

The clinical trial involves **patients** aged 55 to 65 years with an ASA score greater than 3, or patients over 65 years old with any ASA score, who require rapid sequence induction due to being considered to have a full stomach during anesthesia consultation. The study population includes both male and female participants, with no specific restrictions on body mass index (BMI). Participants are undergoing either scheduled or urgent surgery and require general anesthesia in rapid sequence. Relevant lifestyle considerations include the presence of gastro-oesophageal pathology, gastroparesis, a history of bariatric surgery, occlusive syndrome, or failure to adhere to preoperative fasting guidelines. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed to assess the impact of **opioids** on heart rate during rapid sequence intubation. This study is a **double-blind**, randomized, controlled trial involving patients aged 55-65 years with an ASA score greater than 3, or patients over 65 years with any ASA score, who require rapid sequence induction due to a full stomach condition. The trial will utilize **sodium chloride**, **sufentanil citrate**, and **remifentanil** as the investigational products, administered via intravenous injection. The trial is expected to commence on January 2, 2023, and conclude by September 30, 2023, with a maximum treatment period of one day per participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on the principal inclusion criteria, which include age, ASA score, and the requirement for rapid sequence induction. Following the screening, eligible participants will be randomized to receive one of the investigational products. The primary endpoint is the absolute variation in heart rate between the reference value at the entrance into the operating room (T0) and the end of induction and oro-tracheal intubation (T2). Secondary endpoints include various intraoperative parameters such as the Cormack score, laryngoscopy details, and the incidence of intraoperative vomiting or bradycardia.

Participants are expected to be involved in the study for the duration of their surgical procedure, with follow-up assessments conducted to monitor heart rate and other vital signs. The end-of-study visit will occur at the conclusion of the surgical procedure, where final assessments will be made. Conditions that may lead to early termination from the study include withdrawal of consent, adverse events, or any situation where continued participation is deemed unsafe by the investigator. The trial aims to provide valuable insights into the cardiovascular effects of opioids during rapid sequence intubation, contributing to improved anesthetic management in this patient population.

The clinical trial involves the administration of three different treatments, each with specific characteristics and roles within the study. **Sodium Chloride** is utilized as a placebo in this trial. It is provided in the form of a **solution for injection** and is administered via **intravenous injection**. The maximum daily and total dose is 15 ml, with a treatment period limited to one day. Sodium chloride serves as a control to compare the effects of the experimental medications.

**Sufentanil Citrate**, marketed as SUFENTA, is one of the experimental medications used in the trial. It is available as a **solution for injection**, suitable for both intravenous and epidural administration. The maximum daily and total dose is 0.2 µg/kg, administered intravenously. The treatment period is restricted to one day. Sufentanil Citrate is a potent opioid analgesic, and its impact on heart rate during rapid sequence intubation is being evaluated.

**Remifentanil**, marketed as ULTIVA, is another experimental medication in the study. It is provided as a **powder for solution for injection or infusion** and is administered via **intravenous injection**. The maximum daily and total dose is 0.5 µg/kg, with a treatment period of one day. Remifentanil is a short-acting opioid analgesic, and its effects on heart rate during laryngoscopy and intubation are being assessed in this trial.

The efficacy of the clinical trial titled "Impact of opioids on heart rate during rapid sequence intubation: Double-blind randomized controlled study (CANDY-CRASH)" will be assessed using both primary and secondary endpoints. The primary endpoint is the absolute variation of heart rate in beats per minute between T0, which is the reference value at the entrance into the operating room, and T2, the end of induction and oro-tracheal intubation. This measurement will provide a direct assessment of the impact of opioids on heart rate during the intubation process.

Secondary endpoints include a variety of parameters to further evaluate the effects of the intervention. These include the Cormack score, the use of a Macintosh® laryngoscope, and the use of a long bent mandrel for each group. Additionally, the percentage of patients experiencing intraoperative vomiting at T2, requiring vasopressors before T2, and those with thoracic rigidity and/or bradycardia with cardiac output less than 50 beats per minute at T2 will be recorded. Variations in systolic, diastolic, and mean arterial pressures (SAP/DAP and MAP) as well as heart rate (HR) will be assessed at different time points, specifically between T0 and T2, and T0 and T13, with a focus on absolute and relative changes of ±20%.