Morphine Dosing to Prevent Opioid-Induced Hyperalgesia After Remifentanil-Based Thyroidectomy
Administer morphine 0.05-0.1 mg/kg IV (approximately 5-10 mg for a 70-100 kg male) as a single bolus 15-30 minutes before discontinuing remifentanil infusion to prevent acute opioid-induced hyperalgesia and bridge the transition to postoperative analgesia. 1, 2
Understanding the Problem
Remifentanil infusion during thyroidectomy creates a specific challenge: its ultra-short half-life (3-10 minutes) combined with high-dose intraoperative use leads to acute opioid-induced hyperalgesia (OIH) manifesting immediately postoperatively. 3, 4, 2
High-dose remifentanil (>0.2 μg/kg/min) consistently increases postoperative pain scores and morphine requirements compared to lower doses or no remifentanil, with pain scores rising from NRS 5.08 without remifentanil to 6.73 with remifentanil on the day of thyroidectomy. 2
Abrupt remifentanil discontinuation at surgery end produces the worst outcomes, with median pain scores of NRS 50 (0-100 scale) at 30 minutes postoperatively versus NRS 20 when remifentanil is tapered. 1
The hyperalgesic effect is measurable as reduced mechanical pain thresholds near the surgical wound and persists for up to 21 days in animal models, though clinically significant effects in humans appear limited to the immediate postoperative period (first 2-6 hours). 3, 5
Specific Morphine Dosing Strategy
Primary approach: Single transitional dose
Administer morphine 0.05-0.1 mg/kg IV (5-10 mg for typical adult male) 15-30 minutes before anticipated end of surgery while remifentanil is still infusing at reduced rate. 3
This timing allows morphine to reach peak effect (within 20 minutes IV) as remifentanil is discontinued, preventing the analgesic gap that triggers acute withdrawal hyperalgesia. 1
Alternative approach: Remifentanil tapering with morphine
Begin tapering remifentanil from 0.3 μg/kg/min down to 0.1 μg/kg/min over the final 30 minutes of surgery, which reduces 30-minute postoperative pain scores from NRS 50 to NRS 20. 1
Administer morphine 0.05-0.1 mg/kg IV during this tapering period (approximately 20-30 minutes before skin closure) to establish longer-acting analgesia. 1, 2
Multimodal Adjuncts to Reduce Total Opioid Requirements
Intraoperative co-analgesics (these reduce but do not eliminate the need for transitional morphine):
Ketamine 0.5 mg/kg IV bolus can prevent remifentanil-induced hyperalgesia when given before or during remifentanil infusion, though evidence for routine use in thyroidectomy specifically is limited. 3, 5, 6
Dexamethasone 0.15-0.25 mg/kg IV (maximum 8-10 mg) reduces postoperative swelling and has opioid-sparing effects. 3
IV lidocaine infusion (1.5 mg/kg bolus, then 1.5 mg/kg/h) provides additional analgesia and anti-inflammatory effects, though requires cardiac monitoring. 3
Postoperative foundation (start these intraoperatively or in PACU):
Acetaminophen 1000 mg IV or 15 mg/kg IV (whichever is less) every 6 hours, with first dose given intraoperatively. 3, 7
Ketorolac 0.5 mg/kg IV (maximum 30 mg) as single intraoperative dose, or ibuprofen 600-800 mg orally every 6-8 hours starting in PACU if no contraindications. 3, 7
Postoperative Rescue Analgesia Protocol
PACU breakthrough pain management:
Morphine 25-50 μg/kg (2-5 mg) IV boluses titrated to effect every 5-10 minutes until pain controlled to NRS <4. 3
Fentanyl 0.5-1 μg/kg (25-100 μg) IV is an alternative for more rapid onset if immediate rescue needed. 3
Ward-level analgesia:
Oral tramadol 50-100 mg every 4-6 hours as needed for moderate breakthrough pain. 3
Oral oxycodone 5-10 mg every 4-6 hours as needed for severe breakthrough pain, with maximum 5-7 day prescription. 8, 7
Continue scheduled acetaminophen 1000 mg every 6 hours and ibuprofen 600 mg every 6-8 hours for 3-5 days postoperatively. 7
Critical Pitfalls to Avoid
Do not rely solely on remifentanil tapering without transitional opioid - while tapering reduces hyperalgesia compared to abrupt cessation, it does not eliminate the need for longer-acting opioid coverage. 1
Do not wait until PACU to administer first morphine dose - this creates an analgesic gap during remifentanil washout (10-15 minutes) that triggers acute hyperalgesia and higher total opioid requirements. 4, 2
Do not use modified-release opioids (extended-release oxycodone, MS Contin) for postoperative thyroidectomy pain - these are inappropriate for acute pain management and increase risk of oversedation. 3, 8
Do not exceed total morphine equivalents of 50-75 mg in first 24 hours unless pain is truly uncontrolled despite multimodal analgesia, as this suggests inadequate non-opioid foundation or surgical complication. 7
Monitor for opioid-induced ventilatory impairment (OIVI) using sedation scores alongside respiratory rate, especially in first 2 hours postoperatively when morphine peaks and residual remifentanil effects may overlap. 3
Expected Pain Trajectory
Peak pain occurs at 30-45 minutes postoperatively (during PACU stay), then gradually decreases over 6-12 hours with adequate analgesia. 2
By postoperative day 1, pain should be controlled with scheduled non-opioids plus occasional oral opioid rescue (1-2 doses per day maximum). 7
Most patients require no opioids by postoperative day 3-4 when multimodal non-opioid regimen is optimized. 7
If pain intensity increases rather than decreases after day 1, or requires >3 opioid doses daily after day 2, evaluate for surgical complications (hematoma, infection) rather than simply escalating opioids. 7