Complications
Nausea and vomiting should be treated with parenteral antiemetic (e.g., ondansetron), and mixing of acetylcysteine in a flavored drink (e.g., orange juice).
Patients who cannot tolerate oral acetylcysteine can be treated with intravenous acetylcysteine.[84]
Intravenous acetylcysteine administration results in an apparent decrease of vitamin K-dependent clotting factors (II, VII, IX, and X).[112][113] Clotting factors II, VII, IX, and X decrease within 4 hours of starting intravenous acetylcysteine therapy; maximum derangement in factors II, IX, and X occur at 1 hour and factor VII at 4 hours. The effect of intravenous acetylcysteine on clotting factors lasts for the length of the infusion, and it is relatively common for an INR to be 1.2 to 1.3 at the end of therapy, though very rarely >2 times the upper limit of normal, and bleeding is rare.[101]
Flushing, vomiting, rash, pruritus, angioedema, bronchospasm, tachycardia, or hypotension may occur. This is mediated through a nonimmunologic mechanism and is not a true anaphylaxis.[111]
An anaphylactoid reaction was reported in 522 (8.2%) of 6455 acetylcysteine treatment courses in a retrospective medical record review of patients initiated on a 21-hour intravenous acetylcysteine protocol for acetaminophen poisoning.[103] The majority of reactions were cutaneous (n=398; 75.4%).
Urticaria should be managed with diphenhydramine.[100] Intravenous acetylcysteine should be stopped in the presence of angioedema and respiratory symptoms (e.g., bronchospasm); treatment is with diphenhydramine, corticosteroids, and bronchodilators for bronchospasm. Epinephrine may be needed for hypotension.
These reactions are rate- and concentration-dependent. In the absence of symptomatic recurrence, acetylcysteine infusion can be restarted in patients with angioedema and respiratory symptoms at a slower rate 1 hour after the administration of diphenhydramine and symptomatic therapy.[100]
Includes hepatic encephalopathy, sepsis, and gastrointestinal bleeding. Timely referral to a liver unit and assessment of patient candidacy for orthotopic liver transplantation is essential.[58][99]
Acetylcysteine is nearly 100% effective when started within 8 hours after ingestion.[4][85] Treatment delays beyond 8 hours are associated with stepwise increases in risk of hepatotoxicity, transplant, and death.[4][108]
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