Impact of Opioids on Heart Rate During Rapid Sequence Intubation (CANDY-CRASH)

Impact of Opioids on Heart Rate During Rapid Sequence Intubation: Double-blind Randomized Controlled Study

The patient is seen upstream by an anaesthetists resuscitator (MAR) in order to carry out his anesthesia consultation. If the patient meets the eligibility criteria he will be informed of the study and his signed consent will be obtained.

Patients will be divided into 3 parallel groups :

• Group A (placebo +remifentanil)
• Group B (sufentanil + placebo)
• Group C (placebo + placebo)

Constants are taken at T0. A non-invasive continuous monitoring (Clearsight ©) will be used to collect data: blood pressure, heart rate, cardiac output.

To ensure double-blinding the nurse who prepares the syringes is not part of the anesthesia team. He/she numbers them in syringe n°1 and n°2 to indicate the order of injection to the MAR.

The MAR injects the drugs according to the standardized study plan (see below):

• T1: the patient receives an intravenous bolus (IV) over 5 seconds of molecule n°1
• 3 minute delay
• Patient receives Etomidate 0.3 mg/kg IV over 10 seconds
• 5 second delay
• The patient receives an IV bolus over 30 seconds of molecule n°2
• 5 second delay
• The patient receives Succinylcholine or Rocuronium IV over 5 seconds
• T2: End of induction, oro-tracheal intubation (= T2)

The laryngoscopy is performed by an experienced MAR or nurse (IADE). The end of the intubation is defined by the fixation of the intubation tube (T3). Hemodynamic parameters are measured every minute for ten minutes after intubation (T4 to T13).

Maintenance of anesthesia is standardized with halogen gas (SEVOFLURANE) and an opioid (SUFENTANIL). Ten minutes after the patient's intubation (T13), the blind is lifted, allowing the addition of sufentanil in groups A and C before any surgical procedure.

Study Overview

• Status: Terminated
• Conditions: Rapid Sequence Induction
• Intervention / Treatment: Drug: Remifentanil; Drug: Placebo; Drug: Sufentanil

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • France
    • Corbeil-Essonnes, France, France, 91106
      • Centre Hospitalier Sud Francilien

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient over 65 years old and any possible ASA OR Patient aged 55 to 65 years old with an ASA ≥ 3,
• Patient undergoing surgery (urgent or scheduled), requiring general anesthesia in rapid sequence, because considered to have a "full stomach", i.e. with: gastro-oesophageal pathology or gastroparesis or a history of bariatric surgery or food intake within two hours for liquids and within six hours for solids,
• Patient informed of the study who gave their written consent before starting the study procedures,
• Patient affiliated to a French social security system.

Exclusion Criteria:

• Patient < 55 years old,
• Patient on beta blockers,
• Atrial fibrillation or other rhythm or conduction disturbances,
• Patient in hemodynamic failure and/or on catecholamines before the start of GA,
• Patient having a history of stroke, hemorrhagic and/or ischemic and/or transient
• Combination with opioid agonists-antagonists or partial opioid antagonists
• Known hypersensitivity to one of the study drugs or to opioids,
• History of difficult intubation,
• Patient under guardianship, curatorship or deprived of liberty,
• Patient participating in another interventional clinical research,
• Patient under AME (State Medical Aid)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A (placebo + remifentanil)	Drug: Remifentanil; REMIFENTANIL, 5 µg/cc, solution for injection, 0.5 µg/kg, parenteral (intravenous) route, injection delay of 30 seconds, once only; Drug: Placebo; PLACEBO contains 0.9% NaCl, parenteral (intravenous), bolus, one-time
Experimental: Group B (sufentanil + placebo)	Drug: Placebo; PLACEBO contains 0.9% NaCl, parenteral (intravenous), bolus, one-time; Drug: Sufentanil; SUFENTANIL, 5 µg/cc, solution for injection, 0.2 µg/kg, parenteral (intravenous) route, bolus over 5 seconds, once
Placebo Comparator: Group C (placebo + placebo)	Drug: Placebo; PLACEBO contains 0.9% NaCl, parenteral (intravenous), bolus, one-time

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
heart rate beats per minute	Absolute variation of heart rate beats per minute between T0 (reference value at the entrance into the operating room) and T2 (end of induction and oro-tracheal intubation)	T2 : oro-tracheal induction

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cormack score	Cormack score in each group	T2 : oro-tracheal induction
Laryngoscopy of Macintosh number	Laryngoscopy number for each group	T2 : oro-tracheal induction
Use of a long bent mandrel	Use of a long bent mandrel for each group	T2 : oro-tracheal induction
assess side effects according to the opioids used	Percentage of patients with intraoperative vomiting at T2 for each group	T2 : oro-tracheal induction
assess side effects according to the opioids used	Percentage of patients requiring vasopressor before T2	before T2 : oro-tracheal induction
assess side effects according to the opioids used	Percentage of patients with thoracic rigidity and/or bradycardia < 50/min at T2 for each group	T2 : oro-tracheal induction
assess significant variation in hemodynamic responses	Absolute and relative variations of +-20% in SAP/DAP and MAP between T0 and T2	T2 : oro-tracheal induction
assess significant variation in hemodynamic responses	Absolute and relative variations of +/- 20% in SAP/DA and MAP between T0 and T13	T13 (10 minutes after intubation)
assess significant variation in hemodynamic responses	Relative variation of +/- 20% of HR between T0 and T2	T2 : oro-tracheal induction
assess significant variation in hemodynamic responses	Absolute and relative variations of +/- 20% of HR between T0 and T13.	T13 (10 minutes after intubation)

Collaborators and Investigators

• Sponsor: Centre Hospitalier Sud Francilien
• Investigators: Principal Investigator: Marine FONTAINE, MD, Centre Hospitalier Sud Francilien

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2023
• Primary Completion (Actual): October 18, 2023
• Study Completion (Actual): October 18, 2023

Study Registration Dates

• First Submitted: May 17, 2022
• First Submitted That Met QC Criteria: May 19, 2022
• First Posted (Actual): May 20, 2022

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Acids, Acyclic; Carboxylic Acids; Piperidines; Propionates; Fentanyl; Remifentanil; Sufentanil
• Other Study ID Numbers: 2022-501500-10-00

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No