What is the recommended initial effect-site concentration and titration protocol for Remifentanyl (generic name: Remifentanil) using a Target-Controlled Infusion (TCI) model?

Remifentanil Target-Controlled Infusion (TCI) Dosing

For general anesthesia with remifentanil TCI, target an effect-site concentration of 1-3 ng/mL for maintenance, avoiding bolus dosing to prevent respiratory depression, with plasma target concentrations of 3.1-5.3 ng/mL suitable for initial dosing consistent with product label recommendations. 1, 2

Initial Effect-Site Concentration by Clinical Context

General Anesthesia (TIVA)

• Start at 1-3 ng/mL effect-site target for maintenance when combined with propofol TCI (0.5-1 mcg/mL) 1
• Plasma target of ~4 ng/mL achieves drug administration consistent with product label recommendations (0.5-1 μg/kg induction dose and 0.25 μg/kg/min maintenance) across all age groups 2
• Avoid bolus dosing during maintenance to prevent respiratory depression 1

Conscious Sedation for Procedures

• Start at 2 ng/mL effect-site target for flexible fiberoptic bronchoscopy in spontaneously breathing ICU patients, titrating up to maximum 2.5 ng/mL (range 2-4 ng/mL) based on comfort and sedation 3
• EC50 of 2.8 ng/mL (95% CI: 1.8-3.7 ng/mL) provides adequate analgesia in 50% of patients undergoing extracorporeal shock-wave lithotripsy 4

Awake Fiberoptic Intubation

• Start at 0.8 ng/mL effect-site target for awake nasotracheal fiberoptic intubation in cervical trauma patients, providing better vital sign stability and less recall/pain compared to manually controlled infusion 5

Intubation Without Neuromuscular Blockade

• Use 11-19 ng/mL effect-site target (reduced to 6-10 ng/mL after 1 minute) when combined with propofol 6.5 mcg/mL (reduced to 3 mcg/mL after 1 minute) for tracheal intubation without muscle relaxants 6
• 15 ng/mL provides optimal balance, achieving satisfactory intubation in 75% of patients with successful intubation in 95% 6

Age-Specific Modifications

Older Adults (>60 years)

• Use effect-site target of ~2 ng/mL for induction and ~4 ng/mL for starting maintenance to achieve dosages close to product label recommendations 2
• This lower induction target accounts for increased sensitivity in elderly patients 2

All Other Age Groups

• Plasma target of 3.1-5.3 ng/mL is suitable for initial dosing in children, adults, and severely obese individuals 2
• Minor adjustments may be needed based on individual response 2

Critical Safety Considerations

Respiratory Monitoring

• At EC50 (2.8 ng/mL), only 4% probability of respiratory rate <10 with remifentanil TCI, compared to 56% with fentanyl TCI at similar concentrations 4
• Continuous oxygen saturation monitoring is mandatory 7
• Have naloxone (0.1 mg/kg IV) immediately available and be prepared to provide respiratory support 7

Drug Interactions

• Significantly increased risk of apnea when combined with benzodiazepines or other sedatives—exercise extreme caution with co-administration 7
• When combined with propofol, avoid propofol doses exceeding 1.5 mcg/mL to prevent over-sedation and hypoventilation 1

Hemodynamic Management

• Have vasopressors (ephedrine or metaraminol) immediately available to treat hypotension from sympathetic tone ablation 8, 1
• Establish invasive arterial blood pressure monitoring before induction when feasible 1

Withdrawal Risk

• High risk of withdrawal and hyperalgesia after infusion stopped due to remifentanil's ultrashort duration of action (3-10 minutes) 8
• Plan transition to longer-acting opioids before discontinuation 8

Advantages of Remifentanil TCI Over Manual Infusion

• Shorter preparation time and more stable vital signs compared to manually controlled infusion 5
• Less recall and pain during procedures with TCI technique 5
• Easier to use with better intubating conditions 5
• Will not accumulate in kidney/liver dysfunction due to ester metabolism 8

Titration Protocol

• Start at lower end of recommended range (1-2 ng/mL for sedation, 3-4 ng/mL for anesthesia) 1, 2, 3
• Titrate in 0.5 ng/mL increments based on patient response and pain scores 4
• Allow 3-10 minutes for equilibration before assessing effect due to remifentanil's rapid onset 8
• Reduce target concentration after initial induction phase (e.g., from 19 to 10 ng/mL for intubation) 6