52 in 52 – #11: The FAKT Trial
- Sep 10th, 2022
- Christiaan van Nispen
- categories:
Welcome back to the “52 in 52” series. This collection of posts features recently published must-know articles. Our eleventh post looks at the FAKT trial.
Author: Christiaan van Nispen, MD (Emergency Medicine Physician Resident, San Antonio, TX) and Brannon Inman (Chief Resident, Emergency Medicine Physician, San Antonio, TX) // Reviewed by: Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)
Fentanyl versus placebo with ketamine and rocuronium for patients undergoing rapid sequence intubation in the emergency department: A randomized clinical trial
AKA: The “FAKT” Trial
Clinical question:
In patients undergoing rapid sequence intubation (RSI), does the administration of fentanyl immediately before ketamine and rocuronium during rapid sequence intubation (RSI) result in fewer patients with systolic blood pressure (SBP) measurements outside of the 100-150 mm Hg range?
Study design:
- Multi-center, randomized, double-blind, placebo-controlled trial
PICO:
Population:
- 290 adults (age ≥ 18 years) at 5 hospitals in New South Wales, Australia
- Liverpool Hospital (adult and pediatric academic center with 100,000 ED encounters yearly)
- Royal North Shore Hospital (adult and pediatric academic center with 95,000 ED encounters yearly)
- Northern Beaches Hospital (adult and pediatric community hospital with 85,000 ED encounters yearly)
- Campbelltown Hospital (adult and pediatric community hospital with 70,000 ED encounters yearly)
- Orange Health Service (adult and pediatric rural community hospital with 31,000 ED encounters yearly)
- Patients randomized in a 1:1 manner for treatment versus intervention; intention to treat analysis utilized.
- Screened all adult patients requiring RSI for eligibility.
- Excluded:
- Known allergy to fentanyl, ketamine, or rocuronium
- Patients requiring paralysis-only or no-drug intubation
- Patients determined by treating physician to require specific RSI medications
- All patients when the ED was “overwhelmed” (defined as per the opinion of the treating physician or when there was no one trained in the study available to assist, which happened frequently at nighttime)
Intervention:
- 200 micrograms fentanyl in 20 milliliters 0.9% NS; this dose was paired with 2 mg/kg ketamine.
- If treating physician intended to use less than 2 mg/kg ketamine, the volume of the fentanyl syringe injected was decreased proportionately to the reduction in ketamine dose.
Comparator:
- Placebo solution of 20 milliliters of 0.9% NS paired with 2 mg/kg ketamine.
- Volume decreased proportionately with decreased dosing of ketamine, as above.
Management for both groups:
- All patients received ketamine and rocuronium in a standardized dose.
- Preparation for intubation was standardized.
- Additional sedatives in the 10 minutes after intubation were discouraged.
Outcome:
- No significant difference in primary outcome (SBP < 100 or > 150 in the first 10 minutes after administration of RSI medications; note that if baseline blood pressure was outside of this range, further worsening in SBP by ≥ 10% in that direction was used instead).
- Significantly more patients with SBP < 100 in fentanyl group versus significantly more patients with SBP > 150 in placebo group.
- No significant differences in secondary outcomes (first pass success, Cormack-Lehane grade view achieved, hypoxia, ventilator-free days after 30 days, need for surgical or supraglottic airways, cardiac arrest), though the study was insufficiently powered for differences in 30-day mortality.
Randomization:
- Groups relatively balanced in comorbidities, home medications, indications for intubation, pre-intubation resuscitation, ketamine weight-based dose administered, and most baseline vital signs, with the following differences noted:
- 30% of placebo group patients had SBP > 150 mm Hg at baseline versus 24% of fentanyl patients.
- 65% of patients receiving fentanyl were male versus 53% male in placebo group.
Take away:
- Fentanyl decreases the incidence of hypertension during RSI with ketamine, but at the cost of a significant increase in risk of hypotension.
- This is a well-designed, double-blind study performed in the ED.
- Patients were grouped as SBP > 150 with SBP < 100 when calculating the primary outcome, making this a negative trial even though there were significant differences, as above; presumably ED physicians would be more alarmed by an acute blood pressure drop from normal to 85 mm Hg than an elevation from normal to 165 mm Hg.
- A large quantity of patients screened (82 of 476) were excluded due to use of an alternative regimen being required in the opinion of the treating physician; perhaps treating physicians excluded the patients who were most susceptible to harm by hypertension from ketamine or hypotension from fentanyl, affecting secondary outcomes such as mortality or ventilator-free days.
- Grouping of all patients requiring RSI increases external validity, but perhaps there are specific sub-groups of patients requiring RSI who would be most affected by RSI related hypertension and hypotension (for example, patients with hemorrhagic stroke and trauma patients, respectively).
- Extensive use of non-patient centered outcomes, including primary outcome of systolic blood pressure measurement. Several patient-centered outcomes (e.g., mortality) were secondary outcomes, and the long-term clinical significance of hemodynamic changes is not clear.
My take:
I will not routinely administer fentanyl as a component of RSI with ketamine in my clinical practice as hypotension in critically ill patients is associated with increased risk of mortality and other poor clinical outcomes. If I am concerned that ketamine-associated hypertension will result in an adverse outcome, I will use a different sedative.
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.Published online January 22, 2022. doi:10.1111/acem.14446
