Optimal Effect-Site Concentration of Remifentanil to Prevent Intubation Response
For routine intubation with neuromuscular blockade, administer remifentanil 1 mcg/kg as a bolus over 30-60 seconds, which corresponds to an effect-site concentration of approximately 3-5 ng/mL, combined with propofol and a muscle relaxant to achieve optimal intubation conditions while minimizing cardiovascular instability. 1
Evidence-Based Dosing Strategy
Standard Approach with Muscle Relaxants
The FDA-approved dosing demonstrates that remifentanil 1 mcg/kg bolus followed by 0.5 mcg/kg/min infusion provides the best balance of efficacy and safety for preventing intubation responses when combined with propofol and neuromuscular blockade 1. This approach resulted in:
- Only 13-15% response to intubation (compared to 28-30% with comparator opioids) 1
- Minimal hypotension (4% incidence) 1
- Reduced muscle rigidity from 20% to <1% when combined with muscle relaxants 1
Effect-Site Concentration Targets
Research evidence provides more granular effect-site concentration data:
- EC50 (50% response suppression): 3.7-5.0 ng/mL depending on depth of anesthesia 2, 3, 4
- EC95 (95% response suppression): 3.2-3.8 ng/mL with deep anesthesia 4
- Practical target: 3-5 ng/mL for reliable intubation response prevention 2, 3
The Difficult Airway Society recommends target-controlled infusion (TCI) of 1-3 ng/mL effect-site concentration for awake intubation scenarios, though this is a different clinical context requiring lower doses 5, 6
Critical Safety Considerations
Avoid Higher Doses
Do not use remifentanil 2 mcg/kg or higher for routine intubation despite better response suppression, because: 7
- 2 mcg/kg causes 8 minutes of apnea (487 seconds) with 10% still having unacceptable conditions 6, 7
- 4 mcg/kg causes 12.8 minutes of apnea and profound hypotension despite excellent conditions 6, 7
- Rapid administration of even 1 mcg/kg can cause chest wall rigidity 7
Administration Technique
Always administer remifentanil over 30-60 seconds, never as rapid bolus, to prevent muscle rigidity and chest wall stiffness 7, 1. The FDA label explicitly states that administration of propofol or a muscle relaxant prior to or concurrent with remifentanil decreases rigidity incidence from 20% to <1% 1
Algorithmic Approach by Clinical Scenario
Routine Intubation with Muscle Relaxants
- Start remifentanil 1 mcg/kg IV over 30-60 seconds 1
- Immediately follow with propofol 2-2.5 mg/kg 7
- Administer rocuronium or succinylcholine 7
- Maintain with 0.25-0.5 mcg/kg/min infusion post-intubation 1
Patients Requiring Cardiovascular Stability
For neurosurgical, cardiac, or cerebrovascular disease patients, remifentanil is specifically recommended due to superior cough suppression and cardiovascular response attenuation compared to fentanyl 6, 7
Awake Fiberoptic Intubation
Use TCI targeting 1-3 ng/mL effect-site concentration with topical anesthesia 5, 6. Research shows mean concentrations of 6.3-8.06 ng/mL were used successfully, but these higher concentrations are not recommended for routine practice given safety concerns 8
Common Pitfalls to Avoid
- Never use remifentanil as sole induction agent - loss of consciousness cannot be assured and causes high incidence of apnea, rigidity, and tachycardia 1
- Do not give rapid boluses - administer over 30-60 seconds minimum 7, 1
- Remember remifentanil provides zero postoperative analgesia - administer alternative analgesics before discontinuation due to ultra-short context-sensitive half-time 6, 7
- Avoid doses >1 mcg/kg for routine intubation - the FDA label specifically states "initial doses greater than 1 mcg/kg are not recommended" 1
Depth of Anesthesia Considerations
Deeper anesthesia reduces required remifentanil concentration: EC50 was 2.13 ng/mL with burst suppression versus 3.05 ng/mL with normal depth (state entropy 40-60) 4. This suggests that optimizing hypnotic depth can reduce opioid requirements and associated side effects.