Is ipratropium (Inhalation (ipratropium bromide)) effective for treating cough?

Ipratropium for Cough: Evidence-Based Recommendations

Inhaled ipratropium bromide is effective for specific types of cough, particularly post-infectious cough and cough associated with upper respiratory tract infections (URI) or chronic bronchitis, but it is NOT recommended as first-line therapy for chronic cough due to asthma or unexplained chronic cough. 1

When Ipratropium IS Recommended

Post-Infectious Cough (Grade B)

• For adults with post-infectious cough following URI, ipratropium bromide should be considered as first-line therapy as it has been shown to attenuate cough with fair quality evidence and intermediate net benefit 1
• Dosing: 36-80 μg (2 inhalations) four times daily 1, 2
• Clinical response typically occurs within days to weeks, with monitoring for decreased cough frequency and severity 2
• One controlled trial demonstrated significant reduction in both daytime and nighttime cough (P < 0.05), with overall clinical improvement in 12 of 14 patients and complete resolution in 5 patients 3

URI-Associated Cough (Grade A)

• Inhaled ipratropium bromide is the ONLY first-line treatment recommended by ACCP for URI-associated cough with substantial benefit and high-quality evidence 4
• This is the preferred agent over central cough suppressants (codeine, dextromethorphan) which have limited efficacy (Grade D) 4
• Mechanism: blocks muscarinic receptors in airways, reducing bronchospasm and decreasing mucus production with minimal systemic absorption (only 7% absorbed) 1, 2

Chronic Bronchitis (Grade A)

• For stable chronic bronchitis with cough, ACCP strongly recommends ipratropium at 36 μg (2 inhalations) four times daily 2
• Ipratropium is at least as effective as beta-2 agonists in bronchitis patients, though somewhat less effective than beta-2 agonists in asthma 5

When Ipratropium is NOT Recommended

Chronic Cough Due to Asthma

• Inhaled corticosteroids (ICS) should be considered first-line treatment for cough variant asthma, NOT ipratropium 1
• If response to ICS is incomplete, step up ICS dose and consider adding leukotriene inhibitors or beta-agonists in combination with ICS 1
• One study showed ipratropium combined with fenoterol/salbutamol improved cough scores in asthma, but only as adjunctive therapy, not monotherapy 1

Unexplained Chronic Cough (UCC)

• Ipratropium is NOT included in current treatment recommendations for unexplained chronic cough 1
• While one older randomized trial showed significant reduction in cough severity with good safety profile, the findings have not been replicated and the study had small sample size with limited methodological reporting 1
• For UCC, gabapentin is the suggested therapeutic trial after discussing risk-benefit profile 1

Clinical Algorithm for Cough Management

Step 1: Identify the cough type and duration

• Post-infectious cough (3-8 weeks after URI): Consider ipratropium as first-line 1
• Active URI with cough: Use ipratropium as first-line 4
• Chronic bronchitis with cough: Use ipratropium as first-line 2
• Cough due to asthma: Use ICS as first-line, NOT ipratropium 1
• Unexplained chronic cough (>8 weeks): Do NOT use ipratropium 1

Step 2: Dosing and monitoring

• Standard dose: 36-80 μg (2 inhalations) four times daily, maximum 12 doses per day 2, 6
• Monitor for response within days to weeks 2
• Onset of action: 15 minutes to 1.5-2 hours, duration 4-6 hours 5, 6

Step 3: If inadequate response

• For post-infectious cough: Add inhaled corticosteroids if cough persists and adversely affects quality of life 1
• For severe paroxysms: Consider prednisone 30-40 mg daily for short course after ruling out other causes 1
• For chronic bronchitis: Consider combination therapy with beta-2 agonists 2, 5

Important Caveats

• Do NOT use ipratropium for productive cough with sputum as cough serves a physiological function to clear mucus 4
• Ipratropium should NOT be used as single-drug therapy in acute asthmatic exacerbation due to delayed onset of action 6
• Adverse effects are typically mild (dry mouth, cough, nausea, dizziness) and well-tolerated 5, 6, 3
• If cough persists beyond 8 weeks, reconsider the diagnosis and evaluate for upper airway cough syndrome, asthma, or gastroesophageal reflux disease rather than continuing ipratropium 1
• Tiotropium (another long-acting anticholinergic) does NOT suppress cough in COPD patients, highlighting the specific role of ipratropium 1