What is a recommended opioid-sparing regimen for anesthesia and procedural sedation, including medications and their doses?

Opioid-Sparing Approach to Anesthesia and Procedural Sedation

Core Multimodal Regimen

For anesthesia and procedural sedation, implement a multimodal opioid-sparing approach using acetaminophen 1000mg IV, ketorolac 15-30mg IV (or alternative NSAID), ketamine 0.5 mg/kg IV, and dexmedetomidine 0.5-1 mcg/kg loading dose, with propofol or midazolam for sedation, reserving low-dose fentanyl (1 mcg/kg) only for breakthrough needs. 1, 2

This approach prioritizes morbidity and mortality reduction by minimizing opioid-related respiratory depression, postoperative nausea/vomiting, and ileus while maintaining adequate analgesia and sedation. 1

Pre-Procedural Medications (Administered 30-60 Minutes Before)

Non-Opioid Analgesics

• Acetaminophen: 1000mg IV or 15-20 mg/kg in pediatrics 1, 3
• NSAIDs: Ketorolac 15-30mg IV (age-adjusted; reduce dose in elderly and renal impairment) 1
• Gabapentinoids (single dose only): Pregabalin 75-150mg PO (avoid 300mg due to excessive sedation) OR gabapentin 300-600mg PO 1
  • Critical caveat: Use lowest effective dose; higher doses increase sedation, dizziness, and visual disturbances without improving analgesia 1
  • Dose-adjust for elderly and renal dysfunction 1
  • Avoid in patients already receiving chronic gabapentinoids 1

Intra-Procedural Sedation and Analgesia

Primary Sedative Agents

Propofol (preferred for deeper sedation):

• Loading: 0.5-1 mg/kg IV slowly over 1-2 minutes 4
• Maintenance infusion: 25-75 mcg/kg/min (titrate to effect) 4
• Reduce dose by 50% in elderly (>55 years) and ASA III-IV patients 4

Midazolam (for moderate sedation):

• Adults <55 years: 1-2mg IV initially, then 1mg increments every 2 minutes (max usually 6mg total) 1, 5
• Adults >55 years or ASA III-IV: 0.5-1mg IV initially, reduce total dose by 20-50% 1, 5
• Onset: 1-2 minutes; peak effect: 3-4 minutes; duration: 15-80 minutes 1

Opioid-Sparing Adjuncts (Use in Combination)

Ketamine (co-analgesic and MAC reduction):

• Dose: 0.5 mg/kg IV bolus (or 0.25-0.5 mg/kg if using S-ketamine) 2, 6, 7
• Provides analgesia, reduces opioid requirements by 30-50%, and decreases minimum alveolar concentration 2, 7
• Maintains hemodynamic stability and respiratory drive 7

Dexmedetomidine (sympatholysis and sedation):

• Loading dose: 0.5-1 mcg/kg IV over 10 minutes 2, 6, 7
• Maintenance infusion: 0.2-0.7 mcg/kg/hour 7
• Provides anxiolysis, sedation, and opioid-sparing effects without respiratory depression 7
• Caution: May cause bradycardia and hypotension; reduce loading dose in elderly 7

Lidocaine (systemic):

• Loading: 1.5 mg/kg IV 7
• Infusion: 1-2 mg/kg/hour during procedure 7
• Provides analgesia and anti-inflammatory effects 7

Minimal Opioid Use (If Required)

Fentanyl (reserve for breakthrough pain only):

• Minor procedures: 1 mcg/kg IV 2, 6
• Major procedures: Maximum 2 mcg/kg IV 2, 6
• Onset: 1-2 minutes; duration: 30-60 minutes 1
• Dose reduction: 50% or more in elderly patients 1
• Avoid in patients with renal insufficiency (use fentanyl instead of morphine/meperidine) 1, 2

Procedural Sedation Algorithm

Step 1: Pre-medication (30-60 minutes before)

• Acetaminophen 1000mg IV + Ketorolac 15-30mg IV 1
• Consider single-dose pregabalin 75-150mg PO for anxiolysis (if not contraindicated) 1

Step 2: Induction/Initial Sedation

• Option A (Moderate sedation): Midazolam 1-2mg IV + Ketamine 0.5 mg/kg IV 1, 2, 5
• Option B (Deeper sedation): Propofol 0.5-1 mg/kg IV + Ketamine 0.5 mg/kg IV 2, 4
• Add dexmedetomidine 0.5-1 mcg/kg loading dose for enhanced sedation and opioid-sparing 2, 7

Step 3: Maintenance

• Propofol infusion 25-75 mcg/kg/min OR midazolam increments of 1mg every 2-5 minutes 5, 4
• Dexmedetomidine infusion 0.2-0.7 mcg/kg/hour (optional) 7
• Lidocaine infusion 1-2 mg/kg/hour (optional) 7

Step 4: Breakthrough Pain Management

• First line: Ketamine 0.25 mg/kg IV bolus 2
• Second line: Fentanyl 0.5-1 mcg/kg IV (titrate slowly) 2

Post-Procedural Analgesia

• Continue acetaminophen 1000mg IV/PO every 6 hours 1
• Continue NSAID (ketorolac 15-30mg IV every 6 hours or oral alternative) 1
• Avoid routine opioid prescriptions; use only for severe breakthrough pain 1, 8
• If opioids needed: Morphine 2-4mg IV every 4 hours PRN (adults) or 25-50 mcg/kg IV every 4-6 hours (neonates/pediatrics) 3

Critical Safety Considerations

Monitoring Requirements

• Continuous: Pulse oximetry, capnography (strongly recommended), blood pressure, heart rate, respiratory rate 2, 5
• Immediate availability: Naloxone 0.2-0.4mg IV and flumazenil 0.2mg IV for reversal 1, 2
• Oxygen supplementation and airway equipment readily accessible 1, 5

Common Pitfalls to Avoid

1. Synergistic respiratory depression: When combining midazolam with fentanyl, reduce midazolam dose by 50% 1, 5
2. Inadequate pre-medication timing: Administer oral medications 30-60 minutes before procedure to achieve peak effect 1
3. Excessive gabapentinoid dosing: Single lowest dose only (pregabalin ≤150mg); higher doses cause excessive sedation without additional analgesia benefit 1
4. Rapid bolus administration: Always administer sedatives slowly over 1-2 minutes to avoid hypotension and respiratory depression 5, 4
5. Ignoring age-related pharmacokinetics: Reduce all doses by 20-50% in patients >55 years and ASA III-IV 1, 5, 4
6. Benzodiazepine use in elderly: Avoid or minimize benzodiazepines in patients ≥65 years due to increased risk of delirium, cognitive impairment, and falls 1
7. Drug accumulation: Avoid meperidine entirely due to toxic metabolites and poor efficacy 1

Special Populations

Elderly (>65 years):

• Reduce all sedative doses by 50% 1, 5, 4
• Avoid benzodiazepines when possible; prefer dexmedetomidine for anxiolysis 1
• Use lowest effective gabapentinoid dose with caution 1

Renal insufficiency (GFR <30):

• Avoid morphine and meperidine (active metabolite accumulation) 1
• Use fentanyl as preferred opioid if needed 1, 2
• Dose-adjust gabapentinoids significantly 1

Obese patients:

• Calculate doses based on ideal body weight, not actual weight 5, 7
• Consider opioid-free approach with ketamine + dexmedetomidine due to increased sleep apnea risk 7

This evidence-based approach maximizes patient safety by reducing opioid-related morbidity (respiratory depression, PONV, ileus) while maintaining effective analgesia and sedation through multimodal pharmacology. 1, 8, 9