What are the recommended remifentanil infusion rates (micrograms per kilogram per minute) and titration steps for opioid‑naïve adults, opioid‑tolerant patients, elderly or patients with significant hepatic or renal impairment, and children older than one year?

Remifentanil Dosing Guidelines

For opioid-naïve adults undergoing general anesthesia, initiate remifentanil at 0.05-0.2 mcg/kg/min and titrate upward in 0.025 mcg/kg/min increments every 2-5 minutes based on clinical response, with no dose adjustment required for elderly patients or those with hepatic or renal impairment. 1, 2

Standard Adult Dosing for General Anesthesia

Opioid-Naïve Adults

• Starting infusion rate: 0.05-0.2 mcg/kg/min during maintenance anesthesia 1
• Titration increments: 0.025-0.05 mcg/kg/min every 2-5 minutes based on hemodynamic response and surgical stimulation 3
• Typical maintenance range: 0.05-0.3 mcg/kg/min for most surgical procedures 1
• Higher infusion rates up to 0.5-0.75 mcg/kg/min may be required during periods of intense surgical stimulation 3

Intubation Dosing (Without Neuromuscular Blockade)

The Difficult Airway Society provides three distinct approaches: 1

• Low-dose approach: 1-1.5 mcg/kg IV bolus with propofol 2 mg/kg provides acceptable intubation conditions but causes 10% incidence of respiratory depression 1
• High-dose approach: 2 mcg/kg IV bolus with propofol increases apnea time substantially, with 10% unacceptable intubation conditions 1
• Ultra-high dose: 4 mcg/kg IV bolus provides intubation conditions comparable to succinylcholine but causes significant hypotension and prolonged apnea 1

The low-dose approach (1-1.5 mcg/kg) represents the optimal balance between intubation conditions and adverse effects for most patients. 1

Special Populations

Elderly Patients

• No dose reduction required - remifentanil pharmacokinetics remain unchanged with age 2
• However, elderly patients may demonstrate increased pharmacodynamic sensitivity, so monitor hemodynamic responses closely and consider starting at the lower end of the dosing range 2

Hepatic Impairment (Including Severe Liver Disease)

• No dose adjustment necessary - remifentanil clearance is unaffected by hepatic dysfunction because it undergoes esterase metabolism rather than hepatic biotransformation 2
• Patients with severe liver disease show increased sensitivity to ventilatory depression (EC50 of 1.56 ng/ml vs 2.52 ng/ml in controls), though clinical significance is uncertain given remifentanil's ultra-short duration 2
• Use standard dosing but monitor respiratory parameters more closely 2

Renal Impairment (Including End-Stage Renal Disease)

• No dose adjustment required - remifentanil undergoes esterase metabolism with minimal renal clearance and no accumulation of active metabolites 4, 3
• The metabolite GR90291 has minimal opioid activity and does not contribute to clinical effects even if it accumulates 4, 2
• Standard dosing is appropriate for all degrees of renal dysfunction 3

Opioid-Tolerant Patients

• Higher infusion rates will be required to achieve adequate analgesia, though specific dosing recommendations are not established in guidelines 5
• Start with standard dosing and titrate upward more aggressively (larger increments of 0.05-0.1 mcg/kg/min every 2-3 minutes) based on clinical response 5
• Consider adjunctive nonopioid analgesics (ketamine, NSAIDs, acetaminophen) to reduce total opioid requirements 6

Pediatric Dosing (Children >1 Year)

• Intraoperative infusion: 0.05-0.3 mcg/kg/min as recommended by the European Society for Paediatric Anaesthesiology 1
• Starting dose: 0.05-0.1 mcg/kg/min with titration in 0.025 mcg/kg/min increments every 2-5 minutes 1
• Pediatric patients require the same weight-based dosing as adults due to remifentanil's unique esterase metabolism 5

Critical Cardiac Surgery Considerations

During Cardiopulmonary Bypass

• Maintain at least the pre-CPB infusion rate - do not reduce remifentanil during bypass 1

Hypothermia Adjustments

• Reduce dose by 30% after 20-30 minutes at 32°C (mild hypothermia) 1
• Reduce dose by 60% immediately when moderate to deep hypothermia below 28°C is achieved 1

Mandatory Safety Protocols

Monitoring Requirements

• Continuous pulse oximetry and capnography are mandatory when using remifentanil 1, 6
• Monitor blood pressure and heart rate continuously, as remifentanil causes dose-dependent hypotension and bradycardia 3
• Naloxone must be immediately available for reversal of severe respiratory depression 6, 7

Context-Sensitive Half-Time

• Remifentanil's context-sensitive half-time remains 3-4 minutes regardless of infusion duration (even >8 hours), allowing rapid recovery 4, 3
• This contrasts sharply with fentanyl and alfentanil, which accumulate with prolonged administration 1, 4

Critical Pitfall: Postoperative Analgesia Gap

The single most important clinical consideration is that remifentanil provides NO postoperative analgesia due to its ultra-short duration of action. 1, 8, 3

Transition Strategy (Essential)

• Administer a longer-acting opioid (morphine, hydromorphone, or fentanyl) before emergence to prevent an analgesic gap 1
• For procedures with significant postoperative pain, give morphine 0.05-0.1 mg/kg IV or equivalent at least 30-45 minutes before discontinuing remifentanil 1
• Alternative: Reduce remifentanil infusion rate to 0.025-0.05 mcg/kg/min during wound closure while administering multimodal analgesia 8
• Failure to provide transitional analgesia results in severe rebound pain and potential hyperalgesia 1

Multimodal Analgesia

• Combine with acetaminophen 1000 mg IV and ketorolac 15-30 mg IV before emergence 6
• Consider ketamine 0.5 mg/kg IV as a co-analgesic to reduce opioid requirements by 30-50% 6

Drug Interactions

Serotonergic Agents

• When combining remifentanil with serotonergic agents (SSRIs, MAOIs, rasagiline), use the lowest effective dose for the shortest duration with close monitoring for 24-48 hours for serotonin syndrome 1