Hi Laura,
That’s a great question, and I completely understand your hesitation. The traditional teaching has been that paracetamol is contraindicated in liver disease, but more recent evidence, particularly from human medicine, suggests that the reality is more nuanced.
In human patients with chronic liver disease, paracetamol is actually considered the first-line analgesic due to its relatively safer profile compared to NSAIDs and opioids. Prospective studies have shown that even in cirrhosis, therapeutic doses up to four grams per day for thirteen days were well tolerated. The primary concern with hepatotoxicity comes from overdose or in patients with additional risk factors such as alcoholism, fasting, malnutrition or febrile illness, all of which can contribute to glutathione depletion and increase the risk of NAPQI toxicity. Interestingly, studies indicate that the metabolism of paracetamol via glucuronidation and sulfation remains largely intact even in moderate to severe liver disease, with only a slight prolongation of half-life. Importantly, there has been no strong evidence that chronic liver disease itself significantly increases NAPQI production in the absence of other compounding factors.
That being said, the situation in this dog is different from stable chronic liver disease. Here, we are dealing with a confirmed liver neoplasm that, from gross appearance, seems aggressive and malignant, alongside significantly elevated ALT and ALKP. While we do not have a perfect veterinary parallel to human studies on paracetamol in liver disease, the presence of a tumor introduces additional uncertainties. Liver neoplasms, particularly aggressive ones, can disrupt normal hepatic metabolism in unpredictable ways, potentially impairing glucuronidation and glutathione-dependent detoxification of NAPQI. This makes the risk of hepatotoxicity harder to assess.
It is also worth considering that idiosyncratic drug reactions can occur with many medications, including those we otherwise consider safe, and paracetamol is no exception. Most drugs undergo some degree of hepatic and renal metabolism, and while the impact on these organs is usually predictable, unexpected adverse effects do happen. In a compromised liver, even drugs that are typically well tolerated can have altered pharmacokinetics and pharmacodynamics, potentially leading to increased toxicity. This is particularly relevant when hepatic metabolic pathways are already under strain due to disease, inflammation or neoplastic infiltration.
In a dog with stable liver disease and intact synthetic function, I might consider a cautious, low-dose approach with monitoring. However, in this case, given the unknowns surrounding liver function and the already elevated liver enzymes, I would be inclined to avoid paracetamol altogether if possible. There are safer alternatives for analgesia, including gabapentin, amantadine and opioids such as buprenorphine or fentanyl. If paracetamol were absolutely necessary, I would opt for a significantly reduced dose of ten milligrams per kilogram or less with close monitoring of liver function, including synthetic markers like albumin, bile acids and coagulation parameters.
So, while your instincts about paracetamol being contraindicated in hepatic disease are generally correct, the discussion is evolving and there are situations where it can be used safely. However, in this particular case, with a potentially compromised hepatic metabolism due to neoplasia, I would err on the side of caution and look for alternative analgesic options. Given the unpredictability of drug metabolism in compromised livers and the potential for idiosyncratic reactions, a conservative approach seems safest.
Let me know your thoughts. I will ask our anaesthetist, Felipe, for his comments too.
Best,
Scott 🙂
