From the Guidelines
N-acetylcysteine (NAC) should be administered to patients with shock liver as soon as possible to improve liver transplant-free survival and overall survival, as evidenced by recent studies 1. The use of NAC in shock liver is supported by its antioxidant and immunologic effects, which help mitigate liver damage caused by reduced blood flow and subsequent reperfusion injury.
- The recommended dosing regimen for NAC in shock liver is not explicitly stated in the provided evidence, but it is typically administered intravenously at varying doses, with adverse effects including nausea, vomiting, diarrhea, or constipation 1.
- The beneficial effects of NAC on transplant-free survival were found to be closely related to the interval between drug administration and treatment, suggesting that NAC should be started as early as possible 1.
- A recent meta-analysis found that NAC was significantly superior to placebo in reducing hepatotoxicity and mortality in patients with acetaminophen-induced liver failure, and its use has also been suggested to benefit patients with non-acetaminophen-related acute liver failure (ALF) 1.
- The exact mechanisms of action of NAC are not completely understood, but its complex antioxidant and immunologic effects make it a valuable treatment option for managing shock liver, particularly when used as part of a comprehensive approach that includes treating the underlying cause of shock and supporting overall hemodynamics.
From the FDA Drug Label
Acetylcysteine injection is an antidote for acetaminophen overdose indicated to prevent or lessen hepatic injury after ingestion of a potentially hepatotoxic quantity of acetaminophen in patients with an acute ingestion or from repeated supratherapeutic ingestion (RSI) (1). The FDA drug label does not answer the question.
From the Research
Role of NAC in Shock Liver
- N-acetyl cysteine (NAC) has been reported to provide benefit in non-acetaminophen-induced liver failure secondary to infection, drugs, and toxins 2.
- A study found that NAC use in an elderly patient with shock liver secondary to severe sepsis improved liver function, even when liver transplantation was not an option 2.
- NAC has been shown to increase hepatosplanchnic blood flow in experimental settings, and in septic shock patients, it improved the clearance of indocyanine green and the relationship of systemic oxygen consumption to oxygen demand 3.
Mechanism of Action
- NAC increases absolute liver blood flow index and cardiac index, which may suggest enhanced nutritive blood flow 3.
- The increase of liver blood flow index was not caused by redistribution to the hepatosplanchnic area, but by an increase of cardiac index 3.
- NAC has antioxidant effects and can modulate key signaling pathways, making it a potential therapeutic option for the treatment of liver diseases 4.
Comparison with Other Treatments
- N-acetylcysteineamide (NACA) has been compared to NAC in acetaminophen-induced hepatotoxicity, and NACA was found to be more effective in combating oxidative stress and protecting against damage 5.
- Nuciferine (Nuci) has been shown to effectively protect mice against acetaminophen-induced liver injury, with potential mechanisms including amelioration of the inflammatory response and oxidative stress, regulation of APAP metabolism, and activation of autophagy 6.