What multimodal non‑opioid analgesic regimen is appropriate for an 81‑year‑old woman with metastatic pancreatic cancer who reports a pain score of 2/10 but appears to have higher pain, refuses all opioid therapy, is currently on acetaminophen, haloperidol, scopolamine, lorazepam, prochlorperazine, ondansetron and other supportive meds, and has multiple drug allergies including morphine and numerous antibiotics?

Non-Opioid Analgesic Management for Metastatic Pancreatic Cancer

Given this patient's opioid refusal and metastatic pancreatic cancer, you should immediately optimize scheduled acetaminophen to 1000 mg every 6 hours (4000 mg/day maximum), add a scheduled NSAID such as ketorolac 10 mg every 6 hours or ibuprofen 600 mg every 8 hours with gastroprotection, and urgently refer for celiac plexus neurolysis given the pancreatic origin of her pain. 1

Immediate Pharmacologic Optimization

Maximize Current Non-Opioid Analgesics

• Increase acetaminophen from PRN to scheduled dosing at 1000 mg every 6 hours (4000 mg/day total), as the WHO analgesic ladder recommends scheduled around-the-clock dosing rather than PRN for cancer pain, and her current regimen of 500 mg tablets taken PRN is inadequate. 1

• The patient is already on acetaminophen 650 mg suppositories every 6 hours PRN in her comfort pack, which should be converted to scheduled administration if oral route fails. 1

Add Scheduled NSAID Therapy

• Add a scheduled NSAID immediately, as NSAIDs are WHO Level I analgesics that can be combined with acetaminophen for additive effect in cancer pain. 1

• Ketorolac 10 mg PO every 6 hours (maximum 5 days) or ibuprofen 600 mg every 8 hours are appropriate choices, though you must monitor for GI toxicity given her age. 1

• Topical diclofenac gel 1% applied to areas of bony metastases (if present) may provide additional localized pain relief, as recent case reports demonstrate efficacy in pancreatic cancer with vertebral metastases, potentially through both anti-inflammatory and antitumoral mechanisms. 2

• Mandatory gastroprotection with omeprazole 20 mg daily (already prescribed) must continue when NSAIDs are used chronically. 1

Add Adjuvant Analgesics for Neuropathic Component

• Initiate gabapentin 100-300 mg at bedtime, titrating to 1800-3600 mg daily in three divided doses over 7-14 days, as pancreatic cancer pain has a significant neuropathic component from perineural invasion, and gabapentin is first-line for neuropathic cancer pain. 3, 4, 5

• The minimum effective dose is 1800 mg/day, with most patients requiring 1800-3600 mg/day for adequate neuropathic pain relief, so do not abandon treatment before reaching therapeutic dosing. 4

• Titration protocol: Start 300 mg at bedtime × 3 days, then 300 mg BID × 3 days, then 300 mg TID × 3 days, then increase by 300 mg/day every 3 days until reaching 1800 mg/day (600 mg TID), with further increases to 3600 mg/day if needed. 4

• Alternative: Pregabalin 75 mg BID, titrating to 150-300 mg BID, offers simpler dosing and better bioavailability if gabapentin fails or is not tolerated. 4

Urgent Interventional Referral

Celiac Plexus Neurolysis - Priority Intervention

• Refer immediately for EUS-guided celiac plexus neurolysis (EUS-CPN), as this is specifically indicated for pancreatic cancer patients who refuse opioids or cannot achieve adequate analgesia without intolerable side effects. 1, 6

• Celiac plexus block provides targeted pain relief for pancreatic and upper abdominal malignancies by interrupting visceral pain transmission, and is particularly appropriate given her opioid refusal. 1, 6

• This intervention can eliminate or significantly reduce pain in carefully selected pancreatic cancer patients, though relief may be temporary (weeks to months). 1, 6, 5

• Contraindications to assess before referral: coagulopathy, infection, anticoagulation (none listed in her medications), and very short life expectancy. 1

Alternative Interventional Options

• Intrathecal drug delivery systems (IDDS) should be considered if celiac plexus block fails or provides only partial relief, as IDDS can deliver opioids spinally with minimal systemic side effects, potentially overcoming her opioid refusal concerns. 6, 7

• Pancreatic duct stenting may provide analgesia if imaging demonstrates pancreatic duct obstruction, though evidence is limited to case series. 5

Critical Clinical Considerations

Address Pain Assessment Discrepancy

• The discrepancy between her reported 2/10 pain and your objective assessment of higher pain suggests either stoicism, cognitive impairment, or fear of opioid side effects. 1

• Reassess pain using multiple modalities: numeric rating scale, functional impact (sleep, appetite, mobility), and behavioral observations, as self-report may be unreliable in elderly patients with advanced cancer. 1

• Document objective pain indicators: grimacing, guarding, reduced mobility, sleep disturbance, and decreased oral intake. 1

Manage Existing Symptoms

• Her current antiemetic regimen (haloperidol, prochlorperazine, ondansetron) is appropriate for cancer-related nausea, though these medications do not provide analgesic benefit. 1

• Continue scheduled bowel regimen (docusate, bisacodyl, polyethylene glycol) as constipation will worsen with any analgesic escalation. 1, 3

Monitor for Complications

• Pancreatic cancer pain affects 80% of patients with metastatic disease and is associated with reduced survival, making aggressive pain management essential for quality of life. 1, 5, 7

• Renal function must be monitored before and during NSAID therapy given her age (81 years) and concurrent valsartan use, as NSAIDs can precipitate acute kidney injury in elderly patients on ACE inhibitors/ARBs. 4

• Gabapentin requires dose reduction if creatinine clearance falls below 60 mL/min, which is likely in an 81-year-old patient. 4

Common Pitfalls to Avoid

• Do not undertitrate non-opioid analgesics or abandon gabapentin before reaching 1800 mg/day for at least 2 weeks, as premature discontinuation is the most common reason for perceived treatment failure. 4

• Do not delay interventional referral while attempting multiple medication adjustments, as celiac plexus block is specifically indicated for pancreatic cancer and may provide superior analgesia to systemic medications alone. 1, 6

• Do not combine gabapentin with pregabalin, as this provides no additional benefit and increases adverse effects (dizziness, falls). 8

• Do not rush NSAID or gabapentin titration in this 81-year-old patient, as rapid escalation increases fall risk from dizziness and orthostatic hypotension. 4

Realistic Expectations and Follow-Up

• Target pain reduction to ≤4/10 at rest within 2-4 weeks, reassessing every 48-72 hours initially, then weekly. 3

• If pain remains ≥4/10 after optimizing acetaminophen, NSAIDs, and gabapentin to maximum tolerated doses, the patient will likely require opioid therapy or interventional procedures for adequate pain control, as metastatic pancreatic cancer pain is typically severe and progressive. 1, 5

• Document ongoing discussions about opioid therapy, as her refusal may change when non-opioid options prove inadequate for her progressive disease. 1, 5