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. 2026 Jan 16.
doi: 10.1186/s13063-026-09452-6. Online ahead of print.

Best hypnotic drug choice for rapid sequence induction in the operating room: study protocol for a 3-arm superiority open-labeled randomized controlled trial with blinded evaluation of the primary outcome (the HyPnotiKs study)

Nicolas Grillot  1 , Christelle Volteau  2 , Pauline Quillet  3 , Xavier Ambrosi  4 , Anaïs Caillard  5 , Jean-Stéphane David  6 , Alice Blet  7 , Pierre Bouzat  8 , Laurent Blanchet  9 , Nathalie Bruneau  10 , Nidhal Chebbi  11 , Quentin Saint-Genis  12 , Samy Figueiredo  13 , Pierre-Grégoire Guinot  14 , Alexandre Joosten  15 , Morgan Le Guen  16 , François Labaste  17 , Sigismond Lasocki  18 , Mathieu Oudot  19 , Maxime Pommier  17 , Damien Rousseleau  20 , Franck Verdonk  21   22 , Martine Tching-Sin  23 , Elodie Faurel-Paul  3 , Flavien Counille  24 , Charlotte Cossé  24 , Delphine Flattres Duchaussoy  24 , Raphael Cinotti  24 , Antoine Roquilly  24
Affiliations
Free article

Best hypnotic drug choice for rapid sequence induction in the operating room: study protocol for a 3-arm superiority open-labeled randomized controlled trial with blinded evaluation of the primary outcome (the HyPnotiKs study)

Nicolas Grillot et al. Trials. .
Free article

Abstract

Background: Propofol is the most frequently used hypnotic during rapid sequence induction in patients at risk of pulmonary aspiration of gastric contents worldwide. Its most common side effect is to induce hypotension due to dose-dependent vasoplegia. Ketamine is an alternative with pharmacological hemodynamic stability but a higher risk of postoperative delirium. Ketofol, an equimolar combination of these two hypnotics, has recently been proposed in this setting. The objective of this study is to demonstrate the superiority of ketamine (or ketofol) compared to propofol, in association with a neuromuscular blocking agent, for achieving tracheal intubation without hypotension in patients undergoing surgery under general anesthesia and at risk of pulmonary aspiration of gastric contents.

Methods: The HyPnotiKs study is a multicenter, open-labeled, superiority, randomized controlled trial comparing ketamine (2 mg/kg), propofol (2 mg/kg), and ketofol (1 mg/kg each) for rapid sequence induction in 1218 adult surgical patients requiring tracheal intubation during general anesthesia. Enrollment started in April 2025 in 20 French anesthesia units. The expected date of the final follow-up is May 2027. The primary outcome is the proportion of successful tracheal intubation at the first attempt and without major hypotension. A hierarchical procedure is planned to compare the three arms. Intention-to-treat principle will be applied.

Discussion: The HyPnotiKs study protocol has been approved by the ethics committee of the Comité de Protection des Personnes Sud Méditerranée V and will be carried out in accordance with the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentations at scientific conferences and publications in peer-reviewed journals. The HyPnotiKs study is the first randomized controlled trial powered to investigate whether ketamine, ketofol, or propofol is the hypnotic of first choice for rapid sequence induction of anesthesia in patients with a full stomach, considering successful tracheal intubation without hypotension.

Trial registration: ClinicalTrials.gov NCT06733129. Registered on December 2024.

Keywords: Full stomach patient; General anesthesia; Hypotension; Ketamine; Ketofol; Propofol; Rapid sequence induction.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate {24}: The HyPnotiKs trial protocol has been approved by the ethics committee of the Comité de Protection des Personnes Sud Méditerranée V. It will be carried out in accordance with the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. All participants will be informed about the research before any study procedures and will sign a free and informed consent form. Patients are eligible to be enrolled without the provision of legal surrogate consent if they are unable to express consent due to the emergency and if next of kin cannot be informed within the maximum delay for inclusion. Patients who recover sufficient capacity to provide consent will be asked to consent to continue in the trial. The HyPnotiKs study was registered in December 2024 at http://clinicaltrials.gov with trial registration NCT06733129. Consent for publication {32}: Not applicable—no details, images, or videos relating to an individual person have been collected as part of this publication. Competing interests {28}: The authors declare that they have no competing interests related to this research.

References

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