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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Propofol | Active Comparator |
| |
| Ketamine | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Esketamine | Drug | 2 mg per kilogram of body weight |
| |
| Propofol |
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| The number of intubation attempts | The number of intubation attempts | 01 hour |
| The highest heart rate (HR) within one hour after induction | The highest heart rate (HR) within one hour after induction |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Flavia R Machado, MD, PhD | Federal University of São Paulo | Study Chair |
| Raysa Schmidt, MD | Federal University of São Paulo | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Federal University of São Paulo | São Paulo | São Paulo | 04038002 | Brazil |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41870554 | Derived | 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;52(3):476-489. doi: 10.1007/s00134-026-08351-3. Epub 2026 Mar 23. | |
| 41259542 |
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Data will be share after publication upon resonable request
6 months after publication
Upon reasonable request
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| ID | Term |
|---|---|
| C000629870 | Esketamine |
| D015742 | Propofol |
| ID | Term |
|---|---|
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
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| Drug |
1.5 mg per kilogram of body weight |
|
| 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 |
| 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 |
| 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 |
| Derived |
| 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. |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |