From the Guidelines
N-Acetylcysteine (NAC) plays a crucial role in treating acetaminophen overdose by reducing the incidence of hepatotoxicity, hepatic failure, and mortality.
Key Points
- NAC is recommended for patients with acetaminophen overdose, particularly those with hepatotoxicity or suspected hepatotoxicity 1.
- The use of NAC has been shown to decrease disease progression in patients with hepatic failure due to acetaminophen toxicity, regardless of the time of ingestion 1.
- Studies have demonstrated that intravenous NAC reduces mortality, rates of cerebral edema, and the need for inotropic support in patients with hepatic failure 1.
- The Rumack-Matthew nomogram is used to predict hepatic toxicity after an acute acetaminophen ingestion, and NAC treatment is recommended for patients at probable risk 2.
- Early treatment with NAC, within 8-10 hours of ingestion, is associated with a lower incidence of severe hepatotoxicity and mortality 2.
Treatment Guidelines
- Administer NAC to patients with suspected or known acetaminophen overdose, including repeated supratherapeutic ingestions 1.
- Consider NAC treatment for patients with extended-release or repeated supratherapeutic ingestions of acetaminophen, even if the ingestion time is unknown or unreliable 1.
- Use the Rumack-Matthew nomogram to guide treatment decisions, and consider NAC treatment for patients at possible or probable risk for hepatotoxicity 2.
From the Research
Role of N-Acetylcysteine (NAC) in Treating Acetaminophen Overdose
- NAC is used as an antidote to acetaminophen (paracetamol) poisoning, restoring the hepatic glutathione (GSH) pool depleted in the drug detoxification process 3, 4, 5, 6.
- The primary role of NAC as an antioxidant stems from its ability to increase the intracellular concentration of GSH, which is the most crucial biothiol responsible for cellular redox imbalance 4, 5.
- NAC has been shown to be effective in preventing acetaminophen-induced liver injury when administered within 8-24 hours of overdose, regardless of the regimen or route of administration 6.
- The optimal treatment schedule and timing to start treatment with NAC for acetaminophen overdose are crucial, with large variability of NAC regimens found in different studies 6.
Mechanism of Action
- NAC acts as a precursor for the substrate (L-cysteine) in the synthesis of hepatic GSH, depleted through drug conjugation 5.
- NAC's strength is the targeted replenishment of GSH in deficient cells, and it is likely to be ineffective in cells replete in GSH 5.
- NAC can modulate the homeostasis of glutamate, prompting studies of NAC in neuropsychiatric diseases characterized by impaired glutamate homeostasis 3.
Efficacy and Safety
- NAC improves hepatotoxicity and reduces mortality in acetaminophen overdose cases 6.
- The most frequent adverse events reported with NAC administration are anaphylactic reactions, followed by cutaneous and intestinal adverse events 6.
- NAC treatment appears to be safe and tolerable, with further well-designed, larger controlled trials needed for specific psychiatric and neurological disorders where the evidence is favorable 7.