What is an appropriate multimodal analgesic regimen for an adult with acute moderate‑to‑severe pain, considering age, organ function, comorbidities such as renal disease, peptic ulcer disease, bleeding risk, and the need for opioid‑sparing strategies?

Multimodal Analgesia for Acute Moderate-to-Severe Pain in Adults

All adults with acute moderate-to-severe pain should receive scheduled (not as-needed) acetaminophen, an NSAID (unless contraindicated), and gabapentinoids, with regional anesthesia when anatomically feasible, reserving opioids strictly for breakthrough pain. 1

Core Pharmacologic Foundation (Scheduled Dosing)

The following agents should be administered on a fixed schedule to maintain stable serum levels, not as-needed: 1

First-Line Scheduled Agents

• Acetaminophen: 1000 mg every 6 hours (maximum 3000-4000 mg/day), oral or IV 1, 2

  • Reduce maximum to 3000 mg/day in patients >65 years, chronic alcohol use, or hepatic impairment 3
  • Safe in renal disease, making it the preferred analgesic when NSAIDs are contraindicated 4, 3

• NSAIDs (choose one, contraindications detailed below):

  • Ibuprofen 400-800 mg every 6 hours (maximum 2400 mg/day) 1, 4, 3
  • Naproxen 500 mg twice daily 1
  • Celecoxib 200 mg twice daily (preferred if GI risk but no cardiovascular disease) 1
  • Ketorolac 15-30 mg IV/IM every 6 hours (maximum 5 days, maximum 120 mg/day) 5

• Gabapentinoids (especially for neuropathic component or opioid-sparing):

  • Gabapentin: Start 300 mg three times daily, titrate to 900-3600 mg/day in divided doses 1, 3
  • Pregabalin: Start 50-75 mg twice daily, titrate to 150-300 mg twice daily 1, 3

Additional Scheduled Adjuncts

• Dexamethasone: 4-8 mg IV once perioperatively (reduces inflammation and opioid requirements) 2
• Lidocaine patches: Apply to localized painful areas (especially useful in elderly or those with contraindications to systemic agents) 1

Regional Anesthesia (Critical Component)

Regional techniques are mandatory when anatomically appropriate and dramatically reduce opioid requirements: 1

• Peripheral nerve blocks reduce opioid use, pain scores, and hospital length of stay in elderly trauma patients 1
• Fascia iliaca compartment block for hip fractures provides superior analgesia to opioids during movement 1
• Continuous peripheral nerve block infusions extend analgesia duration 1
• Surgical site infiltration with local anesthetics should be performed intraoperatively 2

Opioid Use (Rescue Only, Not Scheduled)

Opioids should be prescribed ONLY for breakthrough pain after the multimodal foundation is established: 1, 2

• Tramadol: 50-100 mg every 6 hours as needed (weaker opioid, preferred first-line rescue) 1, 6
• Oxycodone: 5-10 mg every 4-6 hours as needed (for severe breakthrough pain) 1, 6
• Avoid morphine, hydromorphone, and fentanyl in ambulatory settings when possible 6

Age-Based Opioid Dose Reduction

Reduce opioid doses by 20-25% per decade after age 55, as older patients require fewer opioids for equivalent pain control: 1

• Age 55-64: Reduce by 20-25%
• Age 65-74: Reduce by 40-50%
• Age ≥75: Reduce by 60% or avoid entirely 1

Absolute Contraindications to NSAIDs

NSAIDs must be avoided entirely in the following conditions: 4, 3, 5

• Severe renal impairment: eGFR <30 mL/min or creatinine ≥2× baseline 4, 3
• Active GI bleeding or peptic ulcer disease 4, 3, 5
• Dehydration or volume depletion 4, 5
• Heart failure (NSAIDs cause fluid retention and worsen cardiac function) 3, 5
• Concurrent nephrotoxic medications (aminoglycosides, contrast agents) 4, 5
• Severe cardiovascular disease (unstable angina, recent MI) 4, 3
• Uninterruptible anticoagulation (warfarin, DOACs at therapeutic doses) 4, 3
• Perioperative CABG surgery 3

Mandatory Pre-Treatment Assessment for NSAIDs

Before prescribing any NSAID, assess the following: 4, 3, 5

• Renal function: BUN, creatinine, eGFR (NSAIDs worsen renal function in compromised kidneys) 4, 3
• Age: Patients ≥60 years have 5-6× higher risk of GI bleeding 3, 5
• GI history: Prior peptic ulcer disease carries 5% recurrent bleeding risk within 6 months 3, 5
• Cardiovascular history: Hypertension, coronary disease, stroke 4, 3
• Hydration status: Dehydration increases nephrotoxicity 4, 5
• Concurrent medications: Anticoagulants increase GI bleeding risk 5-6× 3, 5

Alternative Strategy When NSAIDs Are Contraindicated

If NSAIDs cannot be used due to renal disease, peptic ulcer disease, or bleeding risk: 4, 3, 5

• Acetaminophen 1000 mg every 6 hours (maximum 3000-4000 mg/day) as the nonopioid foundation 4, 3
• Gabapentin 300-900 mg three times daily (safe in renal disease with dose adjustment) 1, 3
• Topical NSAIDs (diclofenac gel/patch) for localized pain (minimal systemic absorption) 3, 5
• Tramadol 50-100 mg every 6 hours as needed (opioid-sparing alternative) 1, 6
• Regional anesthesia becomes even more critical when systemic agents are limited 1

Monitoring Requirements During NSAID Use

For patients on NSAIDs beyond 5-10 days, monitor every 3 months: 3, 5

• Blood pressure (NSAIDs increase BP by mean 5 mmHg) 3, 5
• Renal function: BUN, creatinine (discontinue if creatinine doubles) 3, 5
• Liver function tests (discontinue if >3× upper limit of normal) 5
• Complete blood count (monitor for anemia from occult GI bleeding) 3
• Fecal occult blood (screen for GI bleeding) 3

Immediate Discontinuation Criteria

Stop NSAIDs immediately if: 3, 5

• BUN or creatinine doubles from baseline 3, 5
• Hypertension develops or worsens 3, 5
• Signs of acute kidney injury (decreased urine output, rising creatinine, fluid retention) 3, 5
• Any gastrointestinal bleeding 3, 5
• Liver function tests increase >3× upper limit of normal 5

Maximum Duration of NSAID Use

NSAIDs should be limited to the shortest effective duration: 4, 3

• Acute pain: Maximum 5-10 days 4, 3
• Ketorolac: Maximum 5 days (highest GI/renal risk) 5
• Chronic pain: If unavoidable, mandatory monitoring every 3 months 3
• High-risk patients (age >75, renal disease, cardiovascular disease): Maximum 5 days or avoid entirely 4, 3

Special Considerations for High-Risk Populations

Elderly Patients (≥65 Years)

• Reduce ibuprofen to 100 mg/day or avoid entirely in nursing home residents 3
• Prefer acetaminophen as first-line (safer profile) 3, 5
• Reduce opioid doses by 20-25% per decade after age 55 1
• Regional anesthesia is especially beneficial (reduces systemic drug exposure) 1

Renal Disease

• Avoid NSAIDs if eGFR <30 mL/min 4, 3
• Acetaminophen is safe (no renal metabolism) 4, 3
• Gabapentin requires dose reduction (renally cleared): 300 mg daily if eGFR 15-30,300 mg every other day if eGFR <15 3
• Tramadol requires dose reduction: 50 mg every 12 hours if eGFR <30 1

Peptic Ulcer Disease or GI Bleeding Risk

• Avoid NSAIDs entirely if active ulcer or recent bleeding 4, 3, 5
• If NSAID necessary: Use COX-2 inhibitor (celecoxib) + proton pump inhibitor 4, 3
• Acetaminophen + gabapentin + opioids as alternative regimen 3, 5
• Topical NSAIDs (diclofenac gel) for localized pain 3

Bleeding Risk or Anticoagulation

• Avoid NSAIDs if on therapeutic anticoagulation (warfarin, DOACs) 4, 3, 5
• Acetaminophen is safe with anticoagulants 3, 5
• If NSAID necessary: Use lowest dose for shortest duration + PPI, with close monitoring 3, 5

Common Pitfalls to Avoid

• Do NOT use multiple NSAIDs concurrently (e.g., ibuprofen + ketorolac): Toxicities are additive without additional analgesia 5
• Do NOT prescribe NSAIDs "as needed": Scheduled dosing maintains stable levels and superior pain control 1
• Do NOT forget regional anesthesia: It is the most effective opioid-sparing strategy 1
• Do NOT prescribe opioids on a scheduled basis: Use only for breakthrough pain after multimodal foundation 1, 2
• Do NOT ignore "hidden NSAIDs" in combination products (e.g., cold medications) 3
• Do NOT use ibuprofen with low-dose aspirin without proper timing: Take ibuprofen ≥30 minutes after or ≥8 hours before aspirin to avoid blocking cardioprotection 3

Practical Implementation Algorithm

1. Assess contraindications: Renal function, GI history, cardiovascular disease, bleeding risk, age 4, 3, 5

2. Start scheduled foundation:

   • Acetaminophen 1000 mg every 6 hours 1, 2
   • NSAID (if no contraindications): Ibuprofen 400-800 mg every 6 hours OR naproxen 500 mg twice daily 1, 4
   • Gabapentin 300 mg three times daily (titrate up) 1

3. Add regional anesthesia if anatomically feasible 1, 2

4. Prescribe opioids for breakthrough only: Tramadol 50-100 mg every 6 hours as needed (reduce dose by 20-25% per decade after age 55) 1, 6

5. Monitor: BP, renal function, GI symptoms at baseline and every 3 months if NSAID use exceeds 10 days 3, 5

6. Discontinue NSAIDs after 5-10 days or immediately if adverse effects develop 4, 3, 5