What is the recommended approach for using Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and opioids for pain management?

Recommended Approach for NSAIDs and Opioids in Pain Management

First-Line Treatment: NSAIDs and Acetaminophen

For most acute and chronic pain conditions, NSAIDs and/or acetaminophen should be prescribed as first-line therapy before considering opioids. 1, 2

• Acetaminophen and NSAIDs are recommended as first-line agents for musculoskeletal pain, with acetaminophen having fewer side effects than NSAIDs 1
• Standard dosing: acetaminophen 1000 mg every 6 hours (maximum 4 g/day) or ibuprofen 400 mg every 4-6 hours (maximum 2400 mg/day) 3, 4
• The combination of IV acetaminophen and IV NSAIDs provides superior pain control compared to either agent alone without significantly increasing adverse effects 3
• For cancer pain, paracetamol and/or NSAIDs are effective for treating all intensities of pain, at least in the short term unless contraindicated 1

When Opioids Are NOT Recommended First-Line

Opioids should not be prescribed as first-line therapy for chronic neuropathic pain, low back pain, neck pain, musculoskeletal injuries, minor surgeries, dental pain, kidney stones, or headaches including migraine. 1

• The CDC explicitly recommends against opioids as first-line for acute low back pain, with NSAIDs preferred if pharmacologic treatment is chosen 1
• For HIV patients with chronic pain, opioid analgesics should not be prescribed as first-line for long-term management of chronic neuropathic pain due to risks of pronociception, cognitive impairment, respiratory depression, and addiction 1
• Opioids have equivalent or lesser effectiveness for pain relief compared to NSAIDs for many common acute pain conditions 1

Appropriate Opioid Use: Second or Third-Line

Opioids are appropriate as second- or third-line therapy for patients who do not respond to first-line therapies and report moderate to severe pain (rating 4-10). 1

For Acute Severe Pain:

• Opioid therapy has an important role for acute pain related to severe traumatic injuries (crush injuries, burns), invasive surgeries with moderate to severe postoperative pain, and other severe acute pain when NSAIDs are contraindicated or ineffective 1
• Prescribe immediate-release opioids at the lowest effective dose for no longer than the expected duration of severe pain 1
• Prescribe "as needed" rather than scheduled dosing (e.g., hydrocodone 5 mg/acetaminophen 325 mg, one tablet not more frequently than every 4 hours as needed) 1

For Chronic Pain:

• For opioid-naïve patients with moderate pain (rating 4-7), start with nonopioid and adjuvant therapies, then titrate short-acting opioids as needed 1
• For cancer pain with moderate to severe intensity, oral morphine is the opioid of first choice 1
• When opioids are appropriate for chronic neuropathic pain, consider combining morphine with gabapentin for possible additive effects and lower individual doses 1

Opioid Prescribing Algorithm

Step 1: Start with Short-Acting Formulations

• Begin with immediate-release opioids for initial titration 1
• Typical adult regimen: start with the smallest effective dose, combining short- and long-acting opioids 1
• Individual titration using normal release morphine every 4 hours plus rescue doses (up to hourly) for breakthrough pain 1

Step 2: Transition to Long-Acting for Stable Chronic Pain

• Patients with chronic persistent pain managed by stable doses of short-acting opioids should be provided with round-the-clock extended-release or long-acting formulation opioids 1
• Provide rescue doses equivalent to 10-20% of total daily opioid consumption, given every hour as needed during severe exacerbations 1
• Conversion from immediate-release to extended-release formulations must be accompanied by close observation for excessive sedation and respiratory depression 5

Step 3: Titration and Monitoring

• For opioid-tolerant patients with moderate pain, titrate short-acting opioids with the goal of increasing daily dose by 30-50% until pain relief is achieved 1
• Continually reevaluate to assess pain control, adverse reactions, and development of addiction, abuse, or misuse 5
• Routine monitoring is recommended using opioid patient-provider agreements, urine drug testing, pill counts, and prescription drug monitoring programs 1

Critical Safety Considerations

NSAID Precautions:

• Avoid or use NSAIDs with extreme caution in patients with renal disease, GI risk factors, cardiovascular disease, hematologic disorders, or hepatic dysfunction 3, 2
• Absolute contraindications: history of NSAID-associated upper GI bleeding, concurrent anticoagulation, severe renal impairment, acute renal failure, decompensated cirrhosis, or active peptic ulcer disease 3
• Limit ketorolac to maximum 5 days (15-30 mg IV every 6 hours) due to toxicity risks 3, 6
• Monitor baseline and every 3 months: blood pressure, BUN, creatinine, liver function tests, CBC, fecal occult blood 3

Opioid Risk Assessment:

• Assess all patients for risk of misuse, diversion, and addiction prior to prescribing opioids for chronic pain 1
• Consider concurrent conditions including sleep apnea, pregnancy, renal/hepatic insufficiency, mental health conditions, and substance use disorders 1
• Offer naloxone, particularly if patient or household member has overdose risk factors 1
• Use particular caution when prescribing benzodiazepines or other sedating medications concurrently 1

Opioid Adverse Effect Management:

• Start prophylactic stimulating laxatives simultaneously with opioid initiation to prevent opioid-induced constipation 1
• Use metoclopramide or antidopaminergic drugs for opioid-related nausea/vomiting 1

Discontinuation Protocol

Do not abruptly discontinue opioids in physically dependent patients—rapid discontinuation has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. 5

• Initiate taper by small increments (no greater than 10-25% of total daily dose) to avoid withdrawal symptoms 5
• Proceed with dose-lowering at intervals of every 2-4 weeks 5
• Reassess frequently to manage pain and withdrawal symptoms (restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, mydriasis) 5
• If withdrawal symptoms arise, pause the taper or raise the dose to the previous level, then proceed with slower taper 5

Common Pitfalls to Avoid

• Starting with opioids for mild pain exposes patients to unnecessary risks when nonopioids would suffice—always follow the WHO analgesic ladder with stepwise escalation 4
• Using subtherapeutic doses of nonopioids may lead to perceived treatment failure and inappropriate escalation to opioids 4
• Prescribing opioids on a scheduled basis for acute pain rather than "as needed" increases risk of prolonged use 1
• Converting to extended-release formulations without close monitoring for excessive sedation and respiratory depression 5