From the Guidelines
For bronchospasm or hypotension occurring during N-acetylcysteine (NAC) therapy, treatment should be prompt and targeted, prioritizing the patient's morbidity, mortality, and quality of life. The most recent and highest quality study on this topic is from 2019, which provides guidance on the management of suspected immediate perioperative allergic reactions, including refractory anaphylaxis 1. For bronchospasm, immediately stop the NAC infusion and administer a short-acting beta-2 agonist such as albuterol (salbutamol) 2.5-5 mg via nebulizer or 4-8 puffs via metered-dose inhaler with spacer. For persistent symptoms, consider adding ipratropium bromide 0.5 mg via nebulizer.
Key Considerations
- For hypotension, pause the NAC infusion, place the patient supine with legs elevated, and administer IV fluids (500-1000 mL normal saline bolus) as recommended by the 2019 study 1.
- If hypotension persists, vasopressors like norepinephrine (starting at 0.05-0.1 mcg/kg/min) may be necessary, as suggested by the same study 1.
- Once the patient stabilizes, NAC can often be restarted at a slower infusion rate with premedication using diphenhydramine 50 mg IV and, if needed, hydrocortisone 100 mg IV 30 minutes before resuming, to minimize the risk of histamine release and anaphylactoid reactions.
- The use of NAC as a mucolytic agent has been shown to reduce the likelihood of hospitalization and COPD exacerbations, as demonstrated in studies from 2015 and 2017 1.
Management Strategies
- The 2019 study 1 recommends re-evaluation and consideration of additional management strategies after 10 minutes where there is a sustained insufficient response despite adequate dosing of epinephrine and fluids.
- The study also suggests administration of alternative vasopressors such as vasopressin, norepinephrine, metaraminol, or phenylephrine for persistent life-threatening hypotension.
- For persistent life-threatening bronchospasm, the study recommends adding inhaled bronchodilators and considering adding IV bronchodilators.
From the Research
Treatment of Bronchospasm or Hypotension with NAC Therapy for Mucolytic
- The use of N-acetylcysteine (NAC) as a mucolytic agent in the treatment of bronchospasm or hypotension is not well-supported by the provided evidence 2.
- A study published in the Iranian journal of allergy, asthma, and immunology found that the addition of NAC to usual asthma medication had no significant effect in the treatment of asthma exacerbation 2.
- Other studies suggest that the treatment of bronchospasm should involve a multimodal approach, including the use of inhaled beta-2 agonists, systemic corticosteroids, and other agents such as intravenous dexmedetomidine, lidocaine, magnesium, ketamine, and steroids 3, 4.
- The use of albuterol, a long-acting beta 2-adrenergic receptor-selective drug, is commonly recommended for the treatment of bronchospasm, but it may not be effective in all patients and can cause paradoxical bronchoconstriction in some cases 5, 6.
- The management of bronchospasm in the prehospital setting is an important area of research, and studies have identified gaps in current practice, including the underuse of systemic corticosteroids and the need for improved administration of inhaled beta-agonists 3.