In what instances should morphine (opioid) intrathecally and epidurally, as well as Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), including aspirin (acetylsalicylic acid), be avoided or used with caution in asthmatic patients?

NSAIDs and Morphine Use in Asthmatic Patients

Aspirin and COX-1 inhibiting NSAIDs should be used with extreme caution in asthmatics, particularly those with nasal polyps or chronic rhinosinusitis, as they can trigger severe bronchospasm; however, aspirin is NOT an absolute contraindication—it requires risk stratification and potentially formal challenge testing. 1, 2

NSAIDs in Asthma: Risk Stratification

High-Risk Patients (Avoid or Use Only Under Close Supervision)

You should avoid NSAIDs or use them only under direct medical supervision in asthmatics with:

• Severe, poorly controlled asthma 1, 3
• Nasal polyps (classic AERD triad) 1, 2
• Chronic rhinosinusitis 1, 2
• Prior documented reaction to any NSAID 1, 2, 3

The prevalence of aspirin-exacerbated respiratory disease (AERD) is approximately 7-21% in adults with asthma, but can be as low as 0.07% in the general population. 1, 2 The highest suspicion should be in patients with the classic triad: asthma + nasal polyps + NSAID sensitivity. 2

Mechanism and Cross-Reactivity

This is NOT a true IgE-mediated allergy—it's a pseudoallergic reaction from COX-1 inhibition that shunts arachidonic acid metabolism toward the leukotriene pathway. 1, 2 This means:

• High cross-reactivity exists among ALL COX-1 inhibiting NSAIDs (aspirin, ibuprofen, naproxen, indomethacin, diclofenac, ketoprofen) 1, 2, 4
• Low cross-reactivity with selective COX-2 inhibitors (celecoxib, rofecoxib) 1, 2, 4
• Acetaminophen (paracetamol) is the safest alternative at doses <1000mg 2, 4, 3

Safe Alternatives for Asthmatics

When analgesics are needed in high-risk asthmatics:

1. First choice: Acetaminophen ≤1000mg 2, 4, 3
2. Second choice: Selective COX-2 inhibitors (celecoxib)—extremely safe and well-tolerated by almost all aspirin-sensitive asthmatics 2, 4
3. Weak COX-1 inhibitors: Sodium salicylate or choline magnesium trisalicylate 5

When NSAIDs Are Necessary

If an asthmatic with high-risk features requires NSAID therapy:

• Formal aspirin provocation testing should be performed first 2, 3
• Aspirin desensitization followed by daily maintenance therapy can be considered for selected cases, particularly those requiring aspirin for cardiovascular disease 1, 2, 5
• Once desensitized, daily aspirin must be continued indefinitely to prevent resensitization 1, 5

Morphine (Intrathecal and Epidural) in Asthma

Morphine can be safely used intrathecally and epidurally in asthmatics, but requires extreme caution in patients with disorders characterized by hypoxia, as therapeutic doses may decrease respiratory drive while simultaneously increasing airway resistance. 6

Specific Precautions for Neuraxial Morphine

The FDA label for intrathecal morphine states it should be used with extreme caution in patients with disorders characterized by hypoxia, since even usual therapeutic doses may:

• Decrease respiratory drive to the point of apnea 6
• Simultaneously increase airway resistance 6

Clinical Context for Neuraxial Morphine

In the perioperative setting (e.g., cesarean section), intrathecal morphine ≤100μg is recommended and considered safe when:

• Basic analgesics (paracetamol and NSAIDs) are used concurrently 1
• The asthma is well-controlled preoperatively 1
• Appropriate respiratory monitoring is in place 6

For epidural morphine, doses of 2-3mg can be used when spinal anesthesia is not possible. 1

Key Contraindications to Neuraxial Morphine (Not Asthma-Specific)

Hold or avoid neuraxial morphine in:

• Severe hypoxia or respiratory compromise 6
• Increased intracranial pressure or head injury (respiratory depression exaggerated) 6
• Severe hypotension or depleted blood volume 6

Common Pitfalls to Avoid

1. Don't assume all asthmatics are NSAID-intolerant—only 7-21% have AERD, and many can safely use NSAIDs 1, 2
2. Don't rely on skin testing or IgE testing for AERD—these are not useful; diagnosis requires clinical history or formal challenge 2
3. Don't withhold neuraxial morphine solely because of asthma—the concern is hypoxia and respiratory compromise, not asthma per se 6
4. Don't forget that AERD can develop late in life—patients who previously tolerated NSAIDs may develop sensitivity 3
5. Don't use high-dose acetaminophen (>1000mg) in NSAID-sensitive asthmatics without caution—a small proportion may react 4, 3