Background

There is a theoretical risk that patients should receive half dosed sedation agents during intubation if they are hemodynamically unstable. This recommendation was extrapolated from data that propofol and midazolam can cause increasing risk of hypotension with higher doses. However, there is limited evidence on the dose dependent effects on hypotension of etomidate and ketamine. The downside of reducing the sedation dose is that patients may be aware while they are paralyzed and clinicians may not fully resuscitate the patient prior to intubation. There have been multiple small studies done on patient awareness during paralysis in the ED which have some up to 7.4% awareness which can increase risk of PTSD.

This study’s objective was to analyze the incidence of post-intubation hypotension with higher doses of etomidate or ketamine.

Materials/Methods

14,024 RSI from the National Emergency Airway Registry (NEAR)

12,175 (86.8%): etomidate
1,849 (13.2%): ketamine

Pre-data collected on pre-intubation hemodynamics +/- treatment with fluids vs vasopressors Primary outcome: Post-intubation hypotension (SBP <100 mm Hg) within 15 minutes if intubation

Secondary outcome: If post-intubation hypotension occurs, treatment with IV fluids vs vasopressors

Inclusion:

Age >14 years
Orotracheal intubation
Etomidate or Ketamine used for sedation
NEAR date 01/2016 - 12/2018

Exclusion:

Topical anesthesia-facilitated intubation
Missing data related to study variables

Analysis

Linear relationship between sedative drug dose and post-intubation hypotension
Adjusted for confounders (age, sex, difficult airway characteristics)
Multiple sensitivity analyses were done with different combinations of patient characteristics/situation prior to intubation and compared

Results

Postintubation hypotension
- Etomidate: 1,976 (16.2%)
- Ketamine: 537 (29%)
Treated with IV fluids or vasopressors
- Etomidate: 1,521 (12.5%)
- Ketamine: 448 (24.2%)

Outcomes: Sedation dose was not related to post-intubation hypotension and whether or not they were treated with IV fluids or vasopressors after

Sensitivity Analysis Group 1: Excluded patients with hypotension prior to intubation (2,337)

Already hypotensive so outcome isn’t affected by sedation
Etomidate and ketamine dose not associated with postintubation hypotension

Sensitivity Analysis Group 2: Included only patients intubated for shock (1,095)

Population at highest risk for post-intubation hypotension (and theoretically most susceptible to dose-dependent effects of sedation
Etomidate and ketamine dose not associated with postintubation hypotension

Sensitivity Analysis Group 3: Included only patients from EDs who received a standardized dose (20 mg) of etomidate (4,144)

To adjust for the bias from physicians deciding what dose of sedative to administer to patient
Median dose 0.25 mg/kg
Post intubation hypotension occurred in 693 (15.6%)
But it was not associated with etomidate dose
Group 3 subgroup: same as above but excluding patients hypotensive prior to intubation and those intubated for shock
Not associated with postintubation hypotension

Limitations

Physicians chose dose: they may have chosen lower doses for those judged to be at higher risk of hypotension (bias/confounders). However similar results were found in Analysis Group 3.
Did not analyze IBW doses, only actual body weight
Postintubation hypotension was recorded dichotomously (yes/no) vs actual blood pressures so unable to compare absolute BP change
No data on why etomidate vs ketamine was chosen as an induction agent

Discussion/Conclusion

Given lack of association between postintubation hypotension and dose of etomidate or ketamine, this study suggests that more focus should be placed on pre-intubation resuscitation, IV access, volume resuscitation, and vasopressors to prevent it. Decreasing the dose of these sedation agents will likely not help mitigate post-intubation hypotension.

The RAMER Reviews: Sedative Dose for Rapid Sequence Intubation and Post-intubation Hypotension - Is there an Association?