What is the use of N-acetyl cysteine (NAC) as a mucolytic agent in the Intensive Care Unit (ICU)?

From the Guidelines

N-acetyl cysteine (NAC) should be considered as a mucolytic agent in the ICU for patients with respiratory conditions, particularly those with COPD, as it has been shown to reduce the rate of exacerbations and improve lung function, as demonstrated in a large, multicenter study by Zheng et al 1. The use of NAC as a mucolytic agent in the ICU is supported by its mechanism of action, which involves breaking down disulfide bonds in mucus glycoproteins, reducing mucus viscosity and facilitating easier clearance of secretions.

• Key benefits of NAC include:
  • Reduction in the rate of COPD exacerbations, with a relative risk of 0.78 compared to placebo 1
  • Improvement in lung function, as measured by pulmonary function tests 1
  • Well-tolerated, with no significant difference in adverse events compared to placebo 1
• Important considerations when using NAC in the ICU include:
  • Monitoring for potential bronchospasm, particularly in patients with reactive airway disease
  • Pre-treatment with a bronchodilator may be necessary in some cases
  • Assessment of the effectiveness of NAC therapy should be based on improvements in secretion clearance, ventilation parameters, and respiratory status Overall, the use of NAC as a mucolytic agent in the ICU can be a valuable adjunctive therapy for patients with respiratory conditions, particularly those with COPD, and its benefits should be weighed against potential risks and considerations on a case-by-case basis.

From the FDA Drug Label

Acetylcysteine is indicated as adjuvant therapy for patients with abnormal, viscid, or inspissated mucous secretions in such conditions as: Chronic bronchopulmonary disease (chronic emphysema, emphysema with bronchitis, chronic asthmatic bronchitis, tuberculosis, bronchiectasis and primary amyloidosis of the lung) Acute bronchopulmonary disease (pneumonia, bronchitis, tracheobronchitis) Pulmonary complications of cystic fibrosis Tracheostomy care Pulmonary complications associated with surgery Use during anesthesia Post-traumatic chest conditions Atelectasis due to mucous obstruction Diagnostic bronchial studies (bronchograms, bronchospirometry, and bronchial wedge catheterization)

N-acetyl cysteine (NAC) can be used as a mucolytic agent in the Intensive Care Unit (ICU) for patients with abnormal, viscid, or inspissated mucous secretions in various conditions, including chronic bronchopulmonary disease, acute bronchopulmonary disease, pulmonary complications of cystic fibrosis, and post-traumatic chest conditions 2.

• The use of NAC as a mucolytic agent is supported by its indication for adjuvant therapy in patients with mucous secretions.
• However, the label does not explicitly state its use in the ICU setting, but the conditions listed can be applicable to ICU patients.
• Another label confirms the use of Acetylcysteine as a Mucolytic Agent 2.

From the Research

Use of N-Acetyl Cysteine as a Mucolytic Agent in ICU

• N-Acetylcysteine (NAC) is used as a mucolytic agent for the treatment of chronic bronchitis and other pulmonary diseases complicated by the production of viscous mucus 3.
• In the Intensive Care Unit (ICU), NAC has been used as a life-saving mucolytic in cases of critical airway obstruction secondary to solid tracheal mucus plugs 4.
• The use of nebulised NAC has been reported to be effective in preventing imminent cardiorespiratory arrest in patients with pneumonia 4.

Mechanism of Action and Efficacy

• NAC has potent mucolytic, antioxidant, and anti-inflammatory effects, making it a potential treatment for acute lung injury and acute respiratory distress syndrome (ARDS) 5, 6.
• Studies have shown that early administration of NAC may reduce markers of oxidative stress and alleviate inflammation in animal models of acute lung injury and in patients with ARDS or pulmonary infections 5, 6.
• Intravenous NAC has been shown to be superior to placebo and non-inferior to ambroxol in improving sputum viscosity and expectoration difficulty in patients with respiratory disease and abnormal mucus secretion 7.

Safety and Tolerability

• NAC has been reported to have a good tolerability profile, with few mild and transient adverse events noted in published randomised-controlled trials 5, 7.
• The safety and efficacy of orally administered NAC for the management of milder forms of COVID-19 infection within the community setting remains uncertain 5.
• Intravenous NAC has been shown to be well-tolerated, with no new safety concerns identified in a large, multicenter, randomized, controlled study 7.