Propofol Versus Ketamine for Rapid Sequence Intubation in Critically Ill Patients (PROMINE)

Propofol Versus Ketamine for Rapid Sequence Intubation in Critically Ill Patients: A Randomized, Multicenter, Unblinded, Clinical Trial

Rapid-sequence intubation is routinely performed in critically ill patients. It is unclear whether different sedative agents may influence short-term outcomes after intubation, specially hemodynamic stability.

Study Overview

• Status: Completed
• Conditions: Acute Respiratory Failure
• Intervention / Treatment: Drug: Propofol; Drug: Esketamine

Detailed Description

The optimal and safest hypnotic agent for rapid sequence intubation in critically ill patients remains uncertain. Factors such as hypovolemia, vasoplegia, hypoxemia, and acidosis can influence the efficacy and safety of induction agents. Propofol is commonly used for this purpose; however, it is associated with the risk of exacerbating hypotension. Ketamine, which has a more favorable hemodynamic profile, may offer a safer alternative in these patients. Objective: To assess whether ketamine is a safer alternative to propofol for rapid sequence intubation by reducing the incidence of hypotension during induction in critically ill patients.

Methods: This will be a randomized, open-label, pragmatic, bicenter study. A total of 170 critically ill patients requiring endotracheal intubation in the intensive care unit will be randomly assigned to receive either ketamine or propofol as the hypnotic agent. Randomization will be conducted using RedCap with a 1:1 ratio and variable block sizes, stratified by study site and vasopressor use during intubation. Results: The primary outcome will be the occurrence of hypotension, defined as the lowest mean arterial pressure recorded within the first 10 minutes following induction. Secondary outcomes, assessed within 1 hour post-induction, include mortality, incidence of cardiopulmonary arrest, the occurrence of severe hypotension (systolic blood pressure <80mmHg), the occurrence of severe hypoxemia (oxygen saturation < 85%), and the number of intubation attempts. Conclusion: The PROMINE study will provide valuable evidence to guide the selection of hypnotic agents for rapid sequence intubation in critically ill patients. It will contribute to a better understanding of the hemodynamic effects associated with propofol and ketamine in this context, potentially informing clinical practice.

• Study Type: Interventional
• Enrollment (Actual): 207
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • São Paulo
    • São Paulo, São Paulo, Brazil, 04038002
      • Federal University of São Paulo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age above 18 years old
• Physician indicated intubation

Exclusion Criteria:

• Pregnancy
• Intubation during cardiac arrest
• Known of suspected intracranial hypertension
• Know allergy to any of the study drugs (lidocaine, fentanyl, propofol, ketamine, or rocuronium)
• Bradycardia (heart rate below 50 beats per minute) or atrioventricular block without a pacemaker

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine	Drug: Esketamine; 2 mg per kilogram of body weight
Active Comparator: Propofol	Drug: Propofol; 1.5 mg per kilogram of body weight

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lowest mean blood pressure	For the primary outcome, a pre-specified subgroup analysis will evaluate the following groups: patients < 70 versus ≥ 70 years old; patients with a Sequential Organ Failure Assessment (SOFA) score < 8 versus ≥ 8 points; patients on vasopressor versus without vasopressors; and patients with acute respiratory distress syndrome (ARDS) versus those without ARDS. Each subgroup analysis will be performed using linear regression, adjusted for baseline MAP before induction, total vasopressor dose in the first 10 minutes, age, and a random patient intercept. Effect estimates will be reported as mean differences with 95%CIs for each subgroup, with respective interaction p values. We will not adjust for multiplicity.	Ten minutes after induction

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average MAP within the first hour after induction	Average MAP within the first hour after induction	1 hour
Early death	Death within one hour of intubation	01 hour
Cardiac arrest	Cardiac arrest requiring resuscitation	01 hour
Severe hypotension	Systolic blood pressure below 80 mmHg	01 hour
Severe hypoxemia	Peripheral oxygen saturation below 85%	01 hour
Time for successful intubation	Time for successful intubation	01 hour

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The highest heart rate (HR) within one hour after induction	The highest heart rate (HR) within one hour after induction	01 hour
The total dose of vasopressors administered within the first 24 hours, using noradrenaline equivalent dose	Cumulative, in milligrams, dose of vasopressors used	24 hours after intubation
Mean change in vasopressor dose (norepinephrine equivalent) from baseline to hour 1	Mean change in vasopressor dose (norepinephrine equivalent) from baseline to hour 1	01 hour
Ventilator-free days within the first 7 days	Ventilator-free days within the first 7 days, defined as the number of days on which individuals are able to breathe spontaneously without any invasive ventilatory assistance, ascribing zero days to those who die, within 7 days.	07 days
Mortality at day 7	Mortality at day 7	Seven days
ICU mortality	Mortality in the Intensive Care Unit	60 days
Hospital mortality	Mortality in hospital	60 days
The number of intubation attempts	The number of intubation attempts	01 hour
Number of participants with Hypertension, defined as SBP > 180 mmHg	Number of participants with Hypertension, defined as SBP > 180 mmHg Safety outcomes during the first 10 minutes	the first 10 minutes
Number of participants with laryngospasm, as reported by the physician in charge of intubation	Laryngospasm, as reported by the physician in charge of intubation - safety outcome	10 minutes
Number of participants with bradycardia, defined as HR < 45 bpm	Bradycardia, defined as HR < 45 bpm - safety outcome	10 minutes
Number of participants with arrhythmias	Arrhythmias - safety outcome	10 minutes
Number of participants with bronchoaspiration	Bronchoaspiration, defined as the presence of gastric content aspirated into the airway during intubation	10 minutes

Collaborators and Investigators

• Sponsor: Federal University of São Paulo
• Investigators: Principal Investigator: Raysa Schmidt, MD, Federal University of São Paulo; Study Chair: Flavia R Machado, MD, PhD, Federal University of São Paulo

Publications and helpful links

General Publications

• Schmidt RC, Godinho Zampieri F, da Silva Ramos FJ, Santos Cavatoni Serra F, Maccagnan Pinheiro Besen BA, Fonseca Nunes N, Boschetti D, Chohfi Atallah F, Jackiu M, Garcia Melro LM, Nascimento Pontes CD, Vieira Tomotani DY, Petri Damiani L, Rezende de Freitas FG, Ribeiro Machado F; PROMINE Investigators. Propofol versus ketamine in rapid sequence intubation in critically ill patients: a prospective, randomized, controlled trial. Intensive Care Med. 2026 Mar 23. doi: 10.1007/s00134-026-08351-3. Online ahead of print.
• Schmidt RC, Zampieri FG, Ramos FJDS, Serra FSC, Damiani LP, Freitas FGR, Machado FR. Prospective, randomized, controlled trial comparing PROpofol versus KetaMINE in rapid sequence intubation in critically ill patients (PROMINE): protocol paper and statistical analysis plan. Crit Care Sci. 2025 Nov 17;37:e20250133. doi: 10.62675/2965-2774.20250133. eCollection 2025.

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2021
• Primary Completion (Actual): October 31, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: October 13, 2021
• First Submitted That Met QC Criteria: October 13, 2021
• First Posted (Actual): October 25, 2021

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 12, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: ketamine; hypnotics; propofol; airway management; intubation; rapid sequence intubation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Phenols; Benzene Derivatives; Esketamine; Propofol
• Other Study ID Numbers: PROMINE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be share after publication upon resonable request
• IPD Sharing Time Frame: 6 months after publication
• IPD Sharing Access Criteria: Upon reasonable request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No