Best Hypnotic Drug Choice for Rapid Sequence Induction in the Operating Room

Phase 3

Recruiting

• Conditions: Rapid Sequence Induction
• Interventions: Drug: combination of Ketamine and Propofol; Drug: direct IV injection

• Registration Number: NCT06733129
• Lead Sponsor: Nantes University Hospital

Brief Summary

The best hypnotic choice to optimize the balance between good intubation condition quality and hemodynamic stability during RSI performed in the operating theatre remained to be investigated.

Therefore, a randomized study evaluating the efficacy of propofol, ketamine, and a combination of both is appropriate. So, we designed the HyPnotiKs randomized controlled study to investigate the efficacy of these hypnotic drugs in patients undergoing RSI in the operating theatre. The primary endpoint will be the successful tracheal intubation at the first attempt without major arterial hypotension event.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-12-02
• Study First Submitted QC: 2024-12-09
• Study First Posted: 2024-12-13
• Status Verified: 2025-04
• Study Start: 2025-04-14
• Last Update Submitted: 2025-04-22
• Last Update Posted: 2025-04-25
• Primary Completion: 2027-04-14
• Study Completion: 2027-04-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1218

Inclusion Criteria

• age between 18 - 80 years' old

• female* and male

  • ≥ 1 risk factor of aspiration of gastric contents defined as
  • preoperative fasting period of less than 6 hours,
  • occlusive syndrome, functional ileus, vomiting episode within the last 12 hours,
  • orthopaedic trauma within the last 12 hours,
  • medical history of symptomatic gastroesophageal reflux or hiatus, hernia or gastroparesis or dysautonomia or gastroesophageal surgery with sphincter dysfunction)

• patient requiring orotracheal intubation during general anaesthesia in the operating room.

• patient or his/her next of kin written informed consent or emergency procedure

Exclusion Criteria

• predicted impossible tracheal intubation (≥ 1 of the following criteria: patient with known intubation complications, Mallampati score IV, Thyromental Distance ≤ 4.0 cm, Mouth Opening < 3 cm, Sternomental Distance < 12.5 cm, significant modification of the airway due to congenital, cancer, trauma or burning lesions (non-exhaustive list)) [30]

• preoperative arterial hypotension (MAP < 65 mmHg or under catecholamine)

• preoperative respiratory distress syndrome (SpO2 < 90% in room air)

• contraindications to the use of ketamine and/or propofol and/or NMB:

  • allergy to the active substance or to one of the excipients or to soy or peanuts,
  • porphyria
  • intracranial hypertension
  • uncontrolled arterial hypertension (systolic arterial pressure > 180 mmHg)
  • personal or family history of known malignant hyperthermia, congenital muscular dystrophy, myasthenia, a known congenital deficit in plasma pseudocholinesterase

• pregnancy or breast-feeding woman

• patients under court protection or guardianship

• absence of insurance covering health costs

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
KETOFOL	combination of Ketamine and Propofol	Ketofol: combination of Ketamine and Propofol : consecutive direct IV injection of Ketamine 1 mg/kg and Propofol 1 mg/kg after completing pre-oxygenation
KETAMINE	direct IV injection	direct IV injection at dosage of 2 mg/kg after completing pre-oxygenation
PROPOFOL	direct IV injection	direct IV injection at dosage of 2 mg/kg after completing pre-oxygenation.

Primary Outcome Measures

Name	Time	Method
proportion of patients with successful intubation at first attempt and without post-induction hypotension	within 10 minutes after the start of the hypnotic injection	The main objective of the study is to compare the efficacies of ketamine alone and ketamine-propofol combination compared to standard doses of propofol to achieve successful tracheal intubation on the first attempt without hemodynamic hypotension in patients at risk of aspiration of gastric contents in the operating room. The composite primary outcome is the proportion of patients with successful intubation at first attempt and without post-induction hypotension defined by a mean arterial pressure ≤ 60 mmHg within 10 minutes after the start of the hypnotic injection.

Secondary Outcome Measures

Name	Time	Method
rates of tracheal intubation at the first attempt	within 10 minutes after the start of the hypnotic injection	rates of tracheal intubation at the first attempt compared between the three study groups
rates of arterial hypotension episodes	within 10 minutes after the start of the hypnotic injection	rates of arterial hypotension episodes as defined in primary endpoint within 10 minutes after induction of anaesthesia compared between the three study groups
quality of the intubation	within 10 minutes after the start of the hypnotic injection	In the operating theatre (within 10 minutes after the start of the hypnotic injection): Cormack-Lehane score values (from 1 to 4); * Cormack 1: The glottis is seen in its entirety; * Cormack 2: Only the posterior half of the glottis is seen; * Cormack 3: Only a small part of the glottis is seen; * Cormack 4: The glottis is hidden by the epiglottis and tongue.
rates of vasopressor use	within 10 minutes after the start of the hypnotic injection	In the operating theatre (within 10 minutes after the start of the hypnotic injection): rates of vasopressor use
time between administration of hypnotic and tracheal intubation	within 10 minutes after the start of the hypnotic injection	Efficacy of ketamine and / or ketamine-propofol combination compared to standard doses of propofol on the prevention of postoperative complications in the operating theatre (within 10 minutes after the start of the hypnotic injection) : - time between administration of hypnotic (start of anesthetic induction) and tracheal intubation (defined as the 6th capnography curve)
values of heart rate	within 10 minutes after the start of the hypnotic injection	Efficacy of ketamine and / or ketamine-propofol combination compared to standard doses of propofol on the prevention of postoperative complications in the operating theatre (within 10 minutes after the start of the hypnotic injection) : values of heart rate measured every 1 minute from pre-oxygenation to 10 minutes after the start of the hypnotic injection
values of SpO2	within 10 minutes after the start of the hypnotic injection	Efficacy of ketamine and / or ketamine-propofol combination compared to standard doses of propofol on the prevention of postoperative complications in the operating theatre (within 10 minutes after the start of the hypnotic injection): SpO2 measured every 1 minute from pre-oxygenation to 10 minutes after the start of the hypnotic injection
values of blood pressure	within 10 minutes after the start of the hypnotic injection	Efficacy of ketamine and / or ketamine-propofol combination compared to standard doses of propofol on the prevention of postoperative complications in the operating theatre (within 10 minutes after the start of the hypnotic injection): systolic/diastolic/mean blood pressure measured every 1 minute from pre-oxygenation to 10 minutes after the start of the hypnotic injection
rates of pulmonary aspiration of gastric contents	within 10 minutes after the start of the hypnotic injection	Efficacy of ketamine and / or ketamine-propofol combination compared to standard doses of propofol on the prevention of postoperative complications in the operating theatre (within 10 minutes after the start of the hypnotic injection): rates of pulmonary aspiration of gastric contents during the intubation procedure
Tolerance of ketamine and / or ketamine-propofol combination compared to standard doses of propofol	within 7 days after the start of the hypnotic injection	Tolerance of ketamine and / or ketamine-propofol combination compared to standard doses of propofol in the recovery room: Up to day 7: * rates of major cardiovascular complications defined as: cardiac arrest, sustained arrhythmia, myocardial infarction, stroke (total, ischaemic, and haemorrhagic), coronary revascularization or admission to ICU for acute heart failure; * rates of mortality at day 7

Trial Locations

Locations (18)

Chr Angers; 🇫🇷 Angers, France

CH Le Mans; 🇫🇷 Le Mans, France

APHP St-Antoine; 🇫🇷 Paris, France

APHP Tenon; 🇫🇷 Paris, France

CHU Poitiers; 🇫🇷 Poitiers, France

CHRU de Brest Hôpital Cavale Blanche; 🇫🇷 Brest, France

CHU Dijon; 🇫🇷 Dijon, France

CHU Grenoble Alpes; 🇫🇷 Grenoble, France

CHD Vendée; 🇫🇷 La Roche-sur-Yon, France

APHP Bicêtre; 🇫🇷 Le Kremlin-Bicêtre, France

CHU Lille Hopital Salengro; 🇫🇷 Lille, France

CHU Lille Hôpital Claude Huriez; 🇫🇷 Lille, France

CHU Lyon Hôpital Sud; 🇫🇷 Lyon, France

HCL Lyon Croix-Rousse; 🇫🇷 Lyon, France

Chu Nantes (Laennec); 🇫🇷 Nantes, France

Chu Nantes; 🇫🇷 Nantes, France

CHU Toulouse Hôpital Purpan; 🇫🇷 Toulouse, France

CHU Toulouse Hôpital Rangueil; 🇫🇷 Toulouse, France