Propofol Versus Ketamine in Rapid Sequence Intubation in Critically Ill Patients

So I'll start with just some background on the subject.

So rapid sequence intubation or RSI in critically ill patients.

This is a high-risk procedure with a narrow hemodynamic margin.

So RSI combines pre-medication, an induction agent, and neuromuscular blockade, as I'm sure a lot of us are familiar.

Peri-intubation hypotension, severe hypoxemia, and cardiac arrest occur in up to forty-five percent of emergency intubations and are independently associated with increased mortality.

Emergency RSI patients are volume depleted and often catecholamine depleted as well with blunted compensatory reflexes.

So hemodynamic responses to induction agents can differ substantially from our elective OR intubations.

And a lot of this instability is reflecting the underlying shock physiology.

So the induction agent choice is one of our few modifiable contributors.

But the optimal conduction agent, induction agent rather, for critically ill patients remains uncertain, and available drugs have distinct hemodynamic and safety profiles.

So looking at propofol versus ketamine, propofol is mechanistically an allosteric agonist at the GABA A receptor.

It's the most frequently reported induction agent in a twenty-nine country cohort.

It has known myocardial depressant and vasodilatory effects, often, um, because of the reduced sympa-sympathetic and direct inhibition of calcium influx in vascular smooth muscl-muscle, which causes arterial and venous dilation.

And we have observational data on clinically relevant hypotension that's been inconsistent across studies.

Now looking at ketamine, it's mechanistically an NMDA receptor antagonist.

Its popularity is largely based on a presumed hemodynamic advantage, and recent RCT data have challenged the assumption of a clear hemodynamic benefit.

Ketamine is normally sympathomimetic, but in our catecholamine-depleted critically ill patients, as I kinda mentioned earlier, ketamine's direct negative inotropic and vasodilatory effects can predominate.

Now looking at some of the literature that we do have currently, the INTUBE study is one that found that propofol was the induction agent independently associated with cardiovascular instability and collapse.

And we have most recently the RSI trial, which is an RCT that found more cardiovascular collapse with ketamine than with etomidate for RSI in critically ill adults.

So there are no randomized control trials that have directly compared propofol with ketamine, and so that's the gap that the PROMEN trial was designed to address.

So looking at their objective and hypothesis, their objective was to determine whether ketamine reduces the incidence of hypotension during RSI compared with propofol in critically ill adults.

And they hypothesized that ketamine is associated with a lower incidence of hypotension in the first ten minutes following RSI compared with propofol.

So I'll start with just some background on the subject.

So rapid sequence intubation or RSI in critically ill patients.

This is a high-risk procedure with a narrow hemodynamic margin.

So RSI combines pre-medication, an induction agent, and neuromuscular blockade, as I'm sure a lot of us are familiar.

Peri-intubation hypotension, severe hypoxemia, and cardiac arrest occur in up to forty-five percent of emergency intubations and are independently associated with increased mortality.

Emergency RSI patients are volume depleted and often catecholamine depleted as well with blunted compensatory reflexes.

So hemodynamic responses to induction agents can differ substantially from our elective OR intubations.

And a lot of this instability is reflecting the underlying shock physiology.

So the induction agent choice is one of our few modifiable contributors.

But the optimal conduction agent, induction agent rather, for critically ill patients remains uncertain, and available drugs have distinct hemodynamic and safety profiles.

So looking at propofol versus ketamine, propofol is mechanistically an allosteric agonist at the GABA A receptor.

It's the most frequently reported induction agent in a twenty-nine country cohort.

It has known myocardial depressant and vasodilatory effects, often, um, because of the reduced sympa-sympathetic and direct inhibition of calcium influx in vascular smooth muscl-muscle, which causes arterial and venous dilation.

And we have observational data on clinically relevant hypotension that's been inconsistent across studies.

Now looking at ketamine, it's mechanistically an NMDA receptor antagonist.

Its popularity is largely based on a presumed hemodynamic advantage, and recent RCT data have challenged the assumption of a clear hemodynamic benefit.

Ketamine is normally sympathomimetic, but in our catecholamine-depleted critically ill patients, as I kinda mentioned earlier, ketamine's direct negative inotropic and vasodilatory effects can predominate.

Now looking at some of the literature that we do have currently, the INTUBE study is one that found that propofol was the induction agent independently associated with cardiovascular instability and collapse.

And we have most recently the RSI trial, which is an RCT that found more cardiovascular collapse with ketamine than with etomidate for RSI in critically ill adults.

So there are no randomized control trials that have directly compared propofol with ketamine, and so that's the gap that the PROMEN trial was designed to address.

So looking at their objective and hypothesis, their objective was to determine whether ketamine reduces the incidence of hypotension during RSI compared with propofol in critically ill adults.

And they hypothesized that ketamine is associated with a lower incidence of hypotension in the first ten minutes following RSI compared with propofol.