Chest
Volume 129, Issue 1, Supplement, January 2006, Pages 238S-249S
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Supplement
Diagnosis and Management of Cough: ACCP Evidence-Based Clinical Practice Guidelines
Cough Suppressant and Pharmacologic Protussive Therapy: ACCP Evidence-Based Clinical Practice Guidelines

https://doi.org/10.1378/chest.129.1_suppl.238SGet rights and content

Background:

Cough-suppressant therapy, previously termed nonspecific antitussive therapy, incorporates the use of pharmacologic agents with mucolytic effects and/or inhibitory effects on the cough reflex itself. The intent of this type of therapy is to reduce the frequency and/or intensity of coughing on a short-term basis.

Methods:

Data for this review were obtained from several National Library of Medicine (PubMed) searches (from 1960 to 2004), which were performed between May and September 2004, of the literature published in the English language, limited to human studies, using combinations of the search terms “cough,” “double-blind placebo-controlled,” “antitussive,” “mucolytic,” “cough clearance,” “common cold,” “protussive,” “guaifenesin,” “glycerol,” and “zinc.”

Results:

Mucolytic agents are not consistently effective in ameliorating cough in patients with bronchitis, although they may be of benefit to this population in other ways. Peripheral and central antitussive agents can be useful in patients with chronic bronchitis, but can have little efficacy in patients with cough due to upper respiratory infection. Some protussive agents are effective in increasing cough clearance, but their long-term effectiveness has not been established. DNase is not effective as a protussive agent in patients with cystic fibrosis. Inhaled mannitol is acutely effective in this patient population, but its therapeutic potential must be investigated further.

Conclusions:

These findings suggest that suppressant therapy is most effective when used for the short-term reduction of coughing. Relatively few drugs are effective as cough suppressants.

Section snippets

DRUGS THAT AFFECT MUCOCILIARY FACTORS

This topic was not addressed separately in the previous evidence-based guideline.1 In disorders that have associated mucus hypersecretion, cough is elicited to enhance the clearance of accumulated secretions. One pharmacologic approach to treating these disorders is to alter the mucociliary factors. As described by Irwin et al,2 there are several mechanisms by which this may occur, as follows: (1) the drug could be an expectorant, increasing mucus volume; (2) the drug may suppress mucus

RECOMMENDATIONS

1. In patients with chronic bronchitis, agents that have been shown to alter mucus characteristics are not recommended for cough suppression. Level of evidence, good; benefit, none; grade of recommendation, D

2. In patients with cough due to URI or chronic bronchitis, the only inhaled anticholinergic agent that is recommended for cough suppression is ipratropium bromide. Level of evidence, fair; benefit, substantial; grade of recommendation, A

DRUGS THAT AFFECT THE AFFERENT LIMB OF THE COUGH REFLEX

The classification of antitussive drugs as peripheral or central is based largely on preclinical studies. Peripherally acting suppressants lack the sedation potential that is often associated with centrally acting drugs, such as opioids, because they do not penetrate the CNS to an appreciable extent. It should be noted, however, that one centrally acting drug, dextromethorphan, is not sedating, so a central action does not guarantee sedation potential as a side-effect of cough suppression.

RECOMMENDATIONS

3. In patients with chronic or acute bronchitis, peripheral cough suppressants, such as levodropropizine and moguisteine, are recommended for the short-term symptomatic relief of coughing. Level of evidence, good; benefit, substantial; grade of recommendation, A

4. In patients with cough due to URI, peripheral cough suppressants have limited efficacy and are not recommended for this use. Level of evidence, good; benefit, none; grade of recommendation, D

DRUGS THAT AFFECT THE CENTRAL MECHANISM FOR COUGH

This class of compounds is thought to act at one or more sites in the CNS to suppress cough. The particular CNS elements that are sensitive to these drugs are unknown. Based on preclinical experiments,37 the brainstem is thought to be the main region where antitussive agents act by a mechanism in which the motor control of cough is inhibited. However, the production of cough can be associated with sensation, termed the urge to cough, indicating that sensory information associated with cough

RECOMMENDATIONS

5. In patients with chronic bronchitis, central cough suppressants, such as codeine and dextromethorphan, are recommended for the short-term symptomatic relief of coughing. Level of evidence, fair; benefit, intermediate; grade of recommendation, B

6. In patients with cough due to URI, central cough suppressants have limited efficacy for symptomatic relief and are not recommended for this use. Level of evidence, good; benefit, none; grade of recommendation, D

DRUGS THAT AFFECT THE EFFERENT LIMB OF COUGH REFLEX

In this context, the efferent limb of the cough reflex is defined as a spinal action of the drug. While this definition appears to overlap with that of centrally acting drugs, it bears specific attention here. As defined above, our current definition of centrally acting antitussive drugs is restricted to those acting in the brainstem and/or at suprapontine sites. A drug that selectively suppressed the excitability of spinal pathways to abdominal muscle motoneurons would be expected to

RECOMMENDATION

7. In patients with chronic or acute cough requiring symptomatic relief, drugs that affect the efferent limb of the cough reflex are not recommended. Level of evidence, low; benefit, none; grade of recommendation, D

DRUGS THAT AFFECT THE SKELETAL MUSCLES

Neuromuscular blocking agents have been used in conjunction with anesthetics to suppress cough and thus to facilitate intubation. The depolarizing agent, succinylcholine, is most commonly used for this application but has a significant side effect profile.54 Newer non-depolarizing agents have fewer side effects but do not possess the rapid onset and recovery associated with succinylcholine.54, 55, 56 Erhan et al,56 in a double-blind study, showed that anesthetics, especially propofol, can

RECOMMENDATION

8. In patients requiring intubation during general anesthesia, the use of neuromuscular blocking agents is recommended to suppress coughing. Level of evidence, good; benefit, substantial; grade of recommendation, A

OTHER DRUGS

Table 4summarizes studies on the effects of zinc acetate or zinc gluconate on the common cold,58, 59, 60, 61, 62, 63, 64, 65, 66 and two studies63, 67 evaluated cough with subjective measures. Mixed results were obtained, with some studies58, 59, 61, 63, 67 indicating a positive effect of zinc preparations on the common cold and others60, 62, 64, 65, 66 suggesting no benefit. Two metaanalyses68, 69 of these studies have been performed, and both concluded that there was insufficient evidence to

RECOMMENDATIONS

9. In patients with acute cough due to the common cold, preparations containing zinc are not recommended. Level of evidence, good; benefit, none; grade of recommendation, D

10. In patients with acute cough due to the common cold, over the counter combination cold medications, with the exception of an older antihistamine-decongestant, are not recommended until randomized controlled trials prove that they are effective cough suppressants. Level of evidence, fair; benefit, none; grade of

PHARMACOLOGIC PROTUSSIVE THERAPY

Protussive therapy is intended to enhance cough effectiveness to promote the clearance of airway secretions. The most common disorders in which this type of therapy is indicated include cystic fibrosis, bronchiectasis, pneumonia, and postoperative atelectasis.2 In these disorders, mechanical methods to loosen mucus or pharmacologic tools that increase cough clearance may be useful to increase the effectiveness of coughing. Mechanical protussive procedures are covered in another section of this

RECOMMENDATION

12. In patients with neuromuscular impairment, protussive pharmacologic agents are ineffective and should not be prescribed. Level of evidence, good; benefit, none; grade of recommendation, D

PHARMACOLOGIC ENHANCEMENT OF COUGH CLEARANCE

The previous evidence-based guideline1 cited randomized, double-blind, placebo-controlled studies showing that hypertonic saline solution and erdosteine (which is not approved for use in the United States) were effective agents for increasing cough clearance in patients with bronchitis, and that amiloride was effective for this function in patients with cystic fibrosis. Ineffective agents (in bronchitic patients) included carbocysteine, mercaptoethane sulfonate, bromhexine, and guaifenesin.

RECOMMENDATIONS

13. In patients with bronchitis, hypertonic saline solution and erdosteine are recommended on a short-term basis to increase cough clearance. Level of evidence, good; benefit, substantial; grade of recommendation, A

14. In adult patients with cystic fibrosis, amiloride is recommended to increase cough clearance. Level of evidence, good; benefit, substantial; grade of recommendation, A

15. In adult patients with cystic fibrosis, while recombinant DNase does improve spirometry it is not recommended

CONCLUSIONS

Relatively few drugs are effective for the nonspecific suppression of cough. Our current recommendations largely confirm and extend the findings of the previous panel.1 Most notably, the current guidelines expand on the previous consensus by recommending that the use of suppressants be guided by the physician's specific knowledge of the disorder that is eliciting cough.

The previous guideline1 identified a number of different drugs as effective cough suppressants, particularly in patients with

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