Does reduced dose induction agent affect post intubation hypotension?

Post Intubation hypotension has been linked to induction agents, although the studies for this are few. It is moreso related to age and Shock Index. In a registry-based study there was no association between weight-based doses of etomidate and Ketamine and post intubation hypotension(1). In a recent retrospective study, there was no difference between Propofol and Ketamine(2).

"The objective of this study was to determine the hemodynamic associations of ketamine and etomidate after RSI when comparing full- vs reduced-dose induction agent."

The Study

Mattson A E et al. Postintubation hypotension following rapid sequence intubation with full- vs reduced-dose induction agent. Am J health Syst Pharm. 2024 Jul 24:zxae217. doi: 10.1093/ajhp/zxae217. Online ahead of print

Bottom Line

There was no difference found in the rates of post intubation hypotension when using full or reduced doses of Ketamine and Etomidate.

What They Did

This was a retrospective Cohort Study in 6 centres.
They compared the use of Ketamine and Etomidate, whilst excluding Propofol, as it "is less utilized due to its risk of hypotension".

N = 909

Inclusion Criteria

• > 18 years old
• Received Etomidate and Ketamine

Exclusion Criteria

• Patients in cardiac arrest during intubation
• Patients did not authorise their record to be used.

Data Collected included:

• drug and dose of induction and paralytic agents
• pre-intubation shock index
• incidence of hypotension after intubation
• need for treatment of hypotension
• intubation device
• intubation provider
• number of intubation attempts
• patient disposition

Definitions:

• Reduced dose of induction agent was defined as Ketamine at 1.25 mg/kg or less and etomidate of 0.2 mg/kg or less
• Postintubation period was defined as the 30 minutes following intubation.
• Post intubation hypotension was defined as a systolic blood pressure (SBP) of < 100 mm Hg, or in patients with a pre-intubation SBP of < 100 mmHg, a drop in SBP of 20% or more.
• Treatment of hypotension was defined as initiation or increased dose of vasopressors (norepinephrine, epinephrine, phenylephrine, and vasopressin) in the 30 minutes following intubation. 

Primary Outcome: 

The incidence of post-intubation hypotension with, full- and reduced-dose induction agents. 

Secondary Outcomes

• Treatment of hypotension

•  Rate of first-pass intubation success.  

What They Found

• 84% (764/909) of patients received etomidate
• 16% (145/909) received ketamine
• Succinylcholine (n =477; 52.5%) and rocuronium (n = 423; 46.5%) were the main paralytics used.
  • 54.5% of patients receiving full dose etomidate were more likely to receive succinylcholine (54.5%).
    
• Patients who received full-dose ketamine had the lowest mean pre-intubation SBP (106.8 mmHg)
• Those receiving full-dose etomidate had the highest mean SBP (125.4 mm Hg; P ≤ 0.001)
• Shock Index was different in patients receiving different doses of induction agent:
  • Those receiving full-dose etomidate had a shock index of 0.89
  • Those receiving reduced-dose etomidate had a shock index of 0.92
  • Those receiving full-dose ketamine had a shock index of 1.08
  • Those receiving reduced-dose ketamine had a shock index of 1.04 (P = 0.001)
• There was no difference in the incidence of post intubation hypotension for patients receiving full or reduced-dose induction agent (P = 0.73).
  • 23.3%(n = 178) in the etomidate group vs 28.3% (n = 41) in the ketamine group
  • Full-dose ketamine was associated with the highest rate of hypotension (36.5%)
• There was no significant difference in post intubation hypotension between medication dose and  shock index
• Treatment for hypotension occurred in (P = 0.008):
  • 12.5% receiving full-dose and 16.8% receiving reduced-dose etomidate
  • 23.5% receiving full-dose and 25.0% receiving reduced-dose ketamine 

When adjusting for variables patients receiving full-dose ketamine were significantly more likely to have hypotension(OR, 2.56; 95% CI, 1.08-6.25), this was not the case for those receiving full-dose etomidate.

My Take on This

• This was a well done retrospective study, however like many other retrospective studies, is open to selection bias.
• It compared Ketamine and Etomidate
• Dosing cut-offs were used based on weight, which was recorded in the medical notes, however we have no information on how these were derived ie., measured vs estimated weights.
• There was selection bias in this study reflecting a move towards using Ketamine in sicker patients:
  • Patients receiving Ketamine had a higher mean maximum pre-intubation shock index than patients receiving etomidate(1.07 vs 0.89)
  • Patients receiving Ketamine had a lower SBP(107.6 vs 124 mm Hg) and DBP (65.3 vs 73.9 mm Hg), than those receiving etomidate. 
• Vasopressor use at the time of intubation was not included, nor was any inclusion of the use of intravenous fluids.
• We do not know what post-intubation sedation was used, as this may affect blood pressure.

There was no difference found in the rates of post intubation hypotension when using full or reduced doses of Ketamine and Etomidate. The finding of increased rates of post intubation hypotension with full dose Ketamine are not really interpretable, given that patients receiving Ketamine had higher Shock indexes and Lower blood pressures.

This won't change my practice.. I will continue to decide on doses based on each patient's merits.

References

1. Driver BE, et al. Sedative dose for rapid sequence intubation and postintubation hypotension: is
   there an association? Ann Emerg Med. 2023;82(4):417-424. doi:10.1016/j
2. Tamest Z et al. Does the choice of induction agent in rapid sequence intubation in the emergency department influence the incidence of post-induction hypotension? EMA 2024 36, 340-347
   PMID: 38018391