The signs and symptoms of paracetamol toxicity occur in three phases. The first phase begins within hours of overdose, and consists of nausea, vomiting, pallor, and sweating.[12] However, patients often have no specific symptoms or only mild symptoms in the first 24 hours of poisoning. Rarely, after massive overdoses, patients may develop symptoms of metabolic acidosis and coma early in the course of poisoning.[13][14]
The second phase occurs between 24 and 72 hours following overdose and consists of signs of increasing liver damage. In general, damage occurs in hepatocytes as they metabolize the paracetamol. The individual may experience right-upper-quadrant pain. The increasing liver damage also alters biochemical markers of liver function; International normalized ratio (INR) and the hepatic transaminases alanine transaminase and aspartate transaminase rise to abnormal levels.[15] Acute kidney failure may also occur during this phase, typically caused by either hepatorenal syndrome or multiple organ dysfunction syndrome. In some cases, acute kidney failure may be the primary clinical manifestation of toxicity. In these cases, it has been suggested that the toxic metabolite is produced more in the kidneys than in the liver.[16]
The third phase follows at 3 to 5 days, and is marked by complications of massive hepatic necrosis leading to fulminant hepatic failure with complications of coagulation defects, hypoglycemia, kidney failure, hepatic encephalopathy, cerebral edema, sepsis, multiple organ failure, and death.[12] If the third phase is survived, the hepatic necrosis runs its course, and liver and kidney function typically return to normal in a few weeks.[17] The severity of paracetamol toxicity varies depending on the dose and whether appropriate treatment is received.
