Conclusion: There was no difference in rates of systolic blood pressure deviation outside of SBP 100-150 between groups, though SBP tended to be lower in the fentanyl group
My take away: Fentanyl may hold a place in your induction for patients with ICH/vascular emergencies who are already hypertensive, but beware the risk of secondary injury from potential hypotension
- Ketamine is a popular choice for RSI in the ED due to its favourable haemodynamic profile, though there is concern for adverse effects of hypertension particularly in conditions such as intracranial bleeding or vascular emergencies
- Fentanyl is used by some providers as an adjunctive induction medication with ketamine to moderate hypertension, but it may increase the risk of hypotension, which is associated with increased mortality rates
- It is also unclear whether the addition of fentanyl affects intubating conditions or patient-centered outcomes such as mortality
- This was a multi-centre, randomized double-blind placebo controlled trial comparing fentanyl vs placebo in addition to ketamine and rocuronium for RSI in adult ED patients in 5 hospitals in Australia
- Adults ≥ 18yrs were screening for eligibility, and patients were excluded if allergic to study medication, paralysis-only or alternative induction regime was deemed necessary, the ED was overwhelmed or no specialist trained in the protocol was available
- Primary outcome was the proportion of patients in each group with at least 1 SBP measurement outside the prespecified range of 100-150mmHg
- Patients with a SBP ≥ 151 mm Hg prior to induction met the primary outcome if their SBP rose by ≥10%, whereas patients whose SBP at induction was ≤ 99 mm Hg met the primary outcome if their postinduction SBP fell by ≥10%
- Secondary outcomes included first-pass success, hypotension/hypertension, hypoxia, mortality and ventilator-free days
- Prefilled syringes containing either 200mcg fentanyl in 20mL (intervention) or 20mL of 0.9% saline (placebo) were prepared by a third-party compounding service (Baxter Pharmaceutical)
- Ketamine (prepared as 200mg/20mL) was dosed in a weight-based fashion (1-2mg/kg for standard dosing or 0.5-1mg/kg for reduced dosing) and fentanyl was dosed in a 1:1 mL ratio. Rocuronium was dosed at 1.5mg/kg
- e.g. a patient receiving 100mg of ketamine (10mL) would receive 10mL (100mcg) of fentanyl, and a patient receiving 50mg of ketamine (5mL) would receive 5mL (50mcg) of fentanyl
- Drugs were administered in the order of study drug, then ketamine, and then rocuronium in a rapid sequential fashion, with laryngoscopy attempted at 60 seconds after rocuronium bolus
- 302 patients were enrolled with primary outcome data available for 277 patients (142 in fentanyl group vs 148 in placebo group).
- The groups had similar baseline characteristics. Baseline SBP was >150mmHg in 24% of the fentanyl group and 30% of placebo group, and <150mmHg in 7% of both groups. Median SBP were 132mmHg and 135mmHg respectively
- Results: There was no significant difference 66% of patients in the fentanyl group and 65% in the placebo group recording at least 1 SBP reading outside of 100-150mmHg (95% CI -10 to 12, p=0.86)
- Patients in the fentanyl group tended to have lower blood pressures, with 29% having at least one SBP measurement <100mmHg compared to 16% of the placebo group (difference = 13%, 95% CI 3-23), and 69% of the placebo group having a SBP measurement >150 mm Hg compared to 55% of the fentanyl group (difference = 14%, 95% CI 3-24)
- Note this divergence of blood pressure was established by 2-minutes post induction, which suggests that there was no need to pre-dose the fentanyl prior to induction to allow time for effect
- Tachycardia (HR ≥ 120 within 10 min of induction) was more common in the placebo group (48% vs. 61%: difference = 13%, 95% CI = 2 -25)
- There was no difference in other secondary outcomes including first-pass success and 30-day mortality
- There was also no difference in the primary outcome of a planned subgroup analysis of patients receiving <1mg/kg ketamine (61% vs 63%, 95% CI -15 to 19, p=0.82)
- Strengths:
- Adds valuable evidence for clinicians managing patients where opinion on the best induction strategy is rife
- Provides evidence that the addition of fentanyl to ketamine does result in lower blood pressures, even if they remain within to 100-150mmHg range
- Pragmatic study design with a critically ill cohort of ED patients
- Limitations:
- The primary outcome was not patient-centred, and a different primary outcome evaluating degree of SBP change from baseline may be been more useful as a theoretical drop from 149mmHg to 101mmHg may be clinically important
- The dose of fentanyl was matched to the dose of ketamine in this trial, and the ideal dosing to both counteract hypertension and avoid hypotension remains unknown
Reference: Ferguson I, Buttfield A, Burns B et al. Fentanyl versus placebo with ketamine and rocuronium for patients undergoing rapid sequence intubation in the emergency department: The FAKT study-A randomized clinical trial. Acad Emerg Med. 2022 Jun;29(6):719-728
