The correct answer is:

Intravenous administration should be used with extreme caution in patients with asthma.

Educational Objective:

Discuss administration of oral versus intravenous NAC in a high-risk patient (pregnant, with asthma) after acetaminophen overdose.

Key Point:

Oral NAC is preferred in pregnancy and in patients with asthma. The liver rapidly clears oral NCA during first-pass metabolism, which results in higher liver concentration (desired effect, since protective of failing liver), and lower (not higher) concentration to the fetus (desired effect). Intravenous NAC poses an elevated risk of anaphylaxis in patients with asthma and should only be given if the oral route is not an option.

Explanation:

Oral NAC is a safe and effective treatment for acetaminophen toxicity, including for pregnant patients and patients with asthma.

The oral route has essentially no incidence of anaphylactoid reactions, whereas the intravenous route can cause flushing, hives, and angioedema in 16% of patients, and life-threatening bronchospasm in 1%. For this reason, the intravenous route should only be used with extreme caution in patients with asthma (such as the above patient).

In the absence of multi-organ failure, the oral route is also preferred for patients with advanced liver failure (higher concentration of NAC in the liver, which is beneficial).

However, in patients with nausea and vomiting (e.g. during first-stage acetaminophen toxicity), who cannot tolerate oral NAC, receiving the antidote via the intravenous route may be the only option.

The intravenous solution is extremely concentrated and must be diluted to large volumes for pediatric use. This has caused HYPOnatremia in children receiving NAC by the intravenous route (not HYPERnatremia in adults).

Another indication for IV rather than oral NAC is multi-organ failure. NAC appears to be protective not only of the liver, but also of other organs in a poisoned patient with multisystem organ failure and IV administration yields higher concentrations to these other organs.

The therapeutic NAC dosing recommendations for acetaminophen are the same for pregnant and nonpregnant women. However, for pregnant patients, the threshold for a toxic acetaminophen dose is lower than for nonpregnant patients. For pregnant patients, an ingestion 100 mg/kg acetaminophen in 24 hours is considered toxic.

References:

Crowell C. Caring for the mother, concentrating on the fetus: intravenous N-acetylcysteine in pregnancy. Am J Emerg Med. 2008;26:735.e1-2.

Trovato F, et al. Update on the management of acute liver failure. Current Opinion in Critical Care. April 4, 2019. Vol 25.

Hodgman MJ. A review of acetaminophen poisoning. Crit Care Clin. 2012;28:499-516.