Ketamine Shows No Sustained Hemodynamic Advantage Over Propofol During Intubation

Hemodynamic Stability During Rapid Sequence Intubation

Tracheal intubation in the intensive care unit is a high-risk procedure frequently complicated by significant hemodynamic perturbations [1]. Clinicians often prioritize agents like etomidate or ketamine for their perceived cardiovascular stability, yet concerns persist regarding etomidate-induced adrenal suppression and its potential impact on mortality [2, 3]. Rapid sequence intubation in emergency settings requires careful sedative selection to mitigate the risk of post-intubation hypotension, a complication linked to increased morbidity and mortality [4]. While patient-important outcomes such as long-term survival and quality of life are the ultimate goals of critical care, many trials remain focused on immediate physiological parameters [5]. A recent randomized controlled trial now provides data on how the choice between two common induction agents, ketamine and propofol, affects early blood pressure management and downstream outcomes in critically ill adults.

Trial Design and Patient Population

To evaluate the hemodynamic effects of induction agents during emergency airway management, researchers conducted an investigator-initiated, randomized, controlled, open-label trial across two mixed intensive care units. The trial enrolled adults aged 18 years or older who required rapid sequence intubation. Between October 2021 and October 2023, the investigators randomized 207 patients in a 1:1 ratio to receive either ketamine or propofol. Although the open-label design meant clinicians knew which sedative was being administered, the randomization process minimized baseline selection bias. Of the total cohort, 175 patients were included in the modified intention-to-treat analysis (a statistical approach that evaluates participants based on the treatment they actually received, ensuring the findings reflect real-world clinical application). By focusing on this specific population within mixed intensive care units, the study captured a broad range of critical illnesses, providing data directly relevant to the diverse and unstable patient presentations physicians encounter during urgent airway stabilization.

Primary Hemodynamic Outcomes

The researchers defined the primary outcome as the lowest mean arterial pressure (MAP) recorded within the first 10 minutes following induction. To ensure a robust comparison, the analysis utilized a linear regression model (a statistical method that isolates the effect of the drug by controlling for confounding variables). Specifically, the model adjusted for patient age, baseline mean arterial pressure, and the total vasopressor dose administered within that initial 10-minute window. This adjustment is critical for practicing clinicians, as it accounts for pre-existing hemodynamic instability and the pharmacological support required to maintain perfusion during airway management. In the final analysis, the lowest mean arterial pressure within 10 minutes was 66 (55 to 79) mmHg in the ketamine group compared to 60 (48 to 72) mmHg in the propofol group. While ketamine appeared to offer a slight buffer against hypotension, the mean difference in the lowest mean arterial pressure was 6.0 mmHg (95% CI -0.0 to 11.9; p = 0.050). Because this p-value sits exactly at the threshold of statistical significance, the clinical magnitude of this numerical difference remains limited in the immediate post-induction phase. Furthermore, the perceived hemodynamic benefit of ketamine proved to be short-lived. When evaluating the period beyond the immediate induction phase, the average mean arterial pressure difference over the first hour was only 1.67 mmHg (95% CI -1.98 to 5.31). This narrow margin indicates that any initial blood pressure advantage provided by ketamine dissipated rapidly. For the practicing intensivist, these data suggest that the choice of induction agent has minimal impact on sustained hemodynamic stability, as the two drugs resulted in nearly identical pressure profiles throughout the first hour of care.

Cardiovascular Collapse and Mortality Rates

The researchers also evaluated the incidence of acute hemodynamic failure following induction, defining cardiovascular collapse primarily as a required increase in the vasopressor dose within two minutes of the procedure. Under this clinical definition, cardiovascular collapse occurred in 20 out of 91 (22%) ketamine-treated patients compared to 28 out of 84 (33%) patients receiving propofol. While the raw percentage of collapse was lower in the ketamine group, this early physiological advantage did not translate into a survival benefit. The data suggest that while propofol is traditionally associated with more significant vasodilation and myocardial depression, the rapid compensatory vasopressor adjustments made by clinicians at the bedside effectively mitigate the clinical impact of these pharmacological effects. Surprisingly, longer-term outcomes trended toward higher mortality in the ketamine cohort, though these findings did not reach statistical significance. The day-7 mortality was 33% in the ketamine group and 23.8% in the propofol group (OR 1.38; 95% CI 0.86 to 2.24). This trend persisted through the duration of the index hospitalization, where the hospital mortality rate was 60.4% for patients randomized to ketamine and 50.0% for those randomized to propofol (OR 1.21; 95% CI 0.92 to 1.58). These results indicate that the choice of induction agent during rapid sequence intubation does not significantly alter the high baseline mortality risk inherent to critically ill populations. Ultimately, the transient hemodynamic differences observed between ketamine and propofol are unlikely to be the primary drivers of overall patient survival.

Clinical Implications for Sedative Selection

The trial results indicate that while ketamine resulted in a less pronounced decrease in mean arterial pressure in the first 10 minutes compared with propofol, the observed difference was neither clinically meaningful nor sustained. Although the ketamine group maintained a slightly higher minimum mean arterial pressure of 66 mmHg (55 to 79 mmHg) compared to 60 mmHg (48 to 72 mmHg) in the propofol group, this 6.0 mmHg margin (95% CI -0.0 to 11.9; p = 0.050) did not improve downstream outcomes. The rapid equilibration of blood pressure between the two groups, evidenced by an average difference of only 1.67 mmHg (95% CI -1.98 to 5.31) over the first hour, suggests that the initial hemodynamic benefits of ketamine are too transient to alter the clinical trajectory of critically ill patients. These findings challenge sedative selection based solely on the perceived risk of hypotension, a common practice where clinicians avoid propofol in hemodynamically fragile patients due to its known vasodilatory properties. Because the study found no significant difference in hospital mortality (60.4% for ketamine versus 50.0% for propofol; OR 1.21; 95% CI 0.92 to 1.58), the data suggest that the pharmacological choice between a dissociative anesthetic and a GABAergic sedative may be less critical than the overall procedural and hemodynamic management during intubation. The researchers concluded that the current evidence is insufficient to establish a definitive induction agent, highlighting the need for larger trials to determine the optimal pharmacological standard for rapid sequence intubation in the intensive care unit.

References

1. Smischney NJ, Hoskote SS, Moraes AGD, et al. Ketamine/propofol admixture (ketofol) at induction in the critically ill against etomidate (KEEP PACE trial): study protocol for a randomized controlled trial. Trials. 2015. doi:10.1186/s13063-015-0687-0

2. Koroki T, Kotani Y, Yaguchi T, et al. Ketamine versus etomidate as an induction agent for tracheal intubation in critically ill adults: a Bayesian meta-analysis. Critical Care. 2024. doi:10.1186/s13054-024-04831-4

3. Albert SG, Ariyan S, Rather A. The effect of etomidate on adrenal function in critical illness: a systematic review.. Intensive care medicine. 2011. doi:10.1007/s00134-011-2160-1

4. Hellmann RV, Maia IWA, Driver BE, et al. Effect of pretreatment opioids on hemodynamics during emergency intubations: a systematic review.. European journal of emergency medicine : official journal of the European Society for Emergency Medicine. 2025. doi:10.1097/MEJ.0000000000001259

5. Gaudry S, Messika J, Ricard J, et al. Patient-important outcomes in randomized controlled trials in critically ill patients: a systematic review. Annals of Intensive Care. 2017. doi:10.1186/s13613-017-0243-z