In many cases, symptoms may appear after 12 hours of overdose. Signs and symptoms of acetaminophen overdose include the following:

• Pain in the abdomen
• Loss of appetite
• Nausea accompanied by vomiting
• Sweating
• Irritability
• Diarrhea
• Convulsions
• Jaundice
• Confusion
• Blurred vision
• Changes in skin color
• Persistent headache
• Fast heart beat
• Fever accompanied by light headedness
• Passing out blood in urine
• Experiencing difficulty in keeping awake
• Coma

• Gastric Lavage

  There seemed to be no difference between gastric lavage and ipecacuanha, but gastric lavage and ipecacuanha seemed more effective than no treatment (very low quality of evidence). [cochrane.org]

  lavage/whole bowel irrigation supportive care -possible intubation -management of hepatic/renal failure -antiemetics antidote liver transplant gastric lavage/whole bowel irrigation not recommended because APAP is absorbed so quickly N-acetylcysteine [quizlet.com]

  Gastric lavage. Another approach for treatment is gastric lavage in which the content of the stomach are pumped out. The doctor cleans the stomach to empty it from all APAP. Emetics. Emetics are drugs that induce vomit. Acetylcysteine. [med-health.net]

• Malnutrition

  Chronic liver disease Alcoholism HIV/AIDS Malnutrition and prolonged fasting, including living on a very sparse diet like the tea and toast diet Anorexia nervosa Genetic factors Drugs used for epilepsy, mood disorders, certain antibiotics (especially [seniorhealth365.com]

  Chronic overdosage or repeat supratherapeutic doses Mortality is three-fold over the acute Acetaminophen overdosage Concurrent interacting factors: Lowers the threshold for N-Acetylcysteine use (baseline glutathione deficiency) Dehydration, Fastin g or Malnutrition [fpnotebook.com]

  Such conditions might include inherited differences in hepatic enzyme activity, malnutrition, ethanol ingestion, drug interactions, or concomitant medical disorders. [pediatrics.aappublications.org]

  Of course, massive ingestions may be a different kettle of fish… The importance of conditions (e.g. malnutrition, alcoholism, liver disease) that may increase susceptibility to hepatoxicity in the paracetamol overdose is controversial. [lifeinthefastlane.com]

• Fatigue

  One might experience the above symptoms and also blood in urine, fever, dizziness, fainting, hyperventilation, severe fatigue and weakness, desire for food, shaking, blurring of image, increased heart rate, and chronic headache and excessive sleeping, [med-health.net]

  Other rare side effects include yellow skin or eyes, unusual bleeding or bruising, weakness, fatigue, bloody or black stools, bloody or cloudy urine, and a sudden decrease in the amount of urine. [healthofchildren.com]

  Patients with more serious disease (such as hepatitis and necrosis) develop symptoms and signs such as fatigue, weakness, vague abdominal pain, loss of appetite, yellowing of the skin or jaundice due to the accumulation of bilirubin in the blood, itching [emedicinehealth.com]

  Phase 1 0.5-24 hours after ingestion Patients may be asymptomatic or report anorexia, nausea or vomiting, and malaise Physical examination may reveal pallor, diaphoresis, malaise, and fatigue Phase 2 18-72 h after ingestion Patients develop right upper [emedicine.medscape.com]

• Hypothermia

  Haemodialysis is sometimes used for patients with massive acetaminophen overdose when signs of "mitochondrial paralysis" (lactic acidosis, altered mental status, hypothermia and hyperglycaemia) are present. [ncbi.nlm.nih.gov]

  Initial evaluation revealed tachycardia (111/min,) mild hypothermia (95.5 o F,) and a depressed level of consciousness with non-focal neurological examination. Blood glucose was 362 mg/dL. [thepoisonreview.com]

  Acetaminophen poisoning also may present as central nervous system depression, shock, hypothermia, and metabolic acidosis. 42 Because delays in treatment with NAC are associated with worse outcomes, 43, ,44 early treatment is indicated when acetaminophen [pediatrics.aappublications.org]

• Vomiting

  Emetics are medications to induce vomiting in individuals for moving out the drug. Acetylcysteine acts as an antidote which helps in preventing the harmful effects of drug overdose. [symptoma.com]

  Gender: female Suicidal behavior Symptoms Symptoms include: Nausea Vomiting Excessive sweating Pale skin Symptoms of liver failure: Anorexia Nausea Vomiting Malaise Abdominal pain (especially in the upper right portion of the abdomen) Pale skin Excessive [nurseslabs.com]

  The risk of hypokalaemia after acute acetaminophen overdose depends on the extent of acetaminophen exposure, irrespective of N-acetylcysteine administration and independent of whether vomiting occurred. [ncbi.nlm.nih.gov]

  If the patient vomits and is unable to retain the NAC, antiemetics may be administered. [calsprogram.org]

  Characteristic symptoms of liver failure include jaundice (yellowing of the skin and eyes), cola-colored urine, confusion / irritability, low blood sugar, bleeding, nausea and / or vomiting. [schmidtandclark.com]

• Nausea

  The third phase typically begins about 72 hours after ingestion, when the nausea and vomiting reappear and people may look jaundiced and experience confusion or sleepiness. [sharecare.com]

  Gender: female Suicidal behavior Symptoms Symptoms include: Nausea Vomiting Excessive sweating Pale skin Symptoms of liver failure: Anorexia Nausea Vomiting Malaise Abdominal pain (especially in the upper right portion of the abdomen) Pale skin Excessive [nurseslabs.com]

  Characteristic symptoms of liver failure include jaundice (yellowing of the skin and eyes), cola-colored urine, confusion / irritability, low blood sugar, bleeding, nausea and / or vomiting. [schmidtandclark.com]

  Symptoms Symptoms of acetaminophen overdose include fever, weakness, irritability, abdominal pain, vomiting, and nausea, blood in urine, change in skin color, coma, confusion and even death. [symptoma.com]

  Early nonspecific signs that may be present in the first 24 hours include anorexia, nausea, vomiting, or vague abdominal pain. [online.epocrates.com]

• Abdominal Pain

  The factors associated with LS were seen among patients with a history of abdominal pain after ingestion of acetaminophen (p = 0.04), who were on IV-NAC administration (p < 0.001) and had an acutely depressed mood (p = 0.003). [ncbi.nlm.nih.gov]

  Symptoms Symptoms of acetaminophen overdose include fever, weakness, irritability, abdominal pain, vomiting, and nausea, blood in urine, change in skin color, coma, confusion and even death. [symptoma.com]

  Telltale symptoms of an acetaminophen overdose may include abdominal pain, loss of appetite, convulsions, diarrhea, jaundice, and coma. [schmidtandclark.com]

  Gender: female Suicidal behavior Symptoms Symptoms include: Nausea Vomiting Excessive sweating Pale skin Symptoms of liver failure: Anorexia Nausea Vomiting Malaise Abdominal pain (especially in the upper right portion of the abdomen) Pale skin Excessive [nurseslabs.com]

  In stage 2 (after 24 to 72 hours), nausea, vomiting, and abdominal pain may develop. At this stage, blood tests show that the liver is functioning abnormally. In stage 3 (after 3 to 4 days), vomiting becomes worse. [msdmanuals.com]

• Right Upper Quadrant Tenderness

  quadrant abdominal pain, anorexia, nausea, and vomiting Right upper quadrant tenderness may be present Tachycardia and hypotension may indicate volume losses Some patients may report decreased urinary output (oliguria) Phase 3: Hepatic phase 72-96 h [emedicine.medscape.com]

• Persistent Vomiting

  If vomiting persists, or if the patient is unable or unwilling to take NAC orally, protocols for IV administration of NAC are available and appear to be relatively safe, simple, and effective. Contact your poison center for specifics. [calsprogram.org]

• Jaundice

  Acetaminophen-induced liver function abnormalities were characterized by elevation of transaminase levels with ALT higher than AST(6/6), coagulopathy(5/6), thrombocytopenia (1/6), but absence of jaundice(6/6). [ncbi.nlm.nih.gov]

  The third phase typically begins about 72 hours after ingestion, when the nausea and vomiting reappear and people may look jaundiced and experience confusion or sleepiness. [sharecare.com]

  Telltale symptoms of an acetaminophen overdose may include abdominal pain, loss of appetite, convulsions, diarrhea, jaundice, and coma. [schmidtandclark.com]

  Suicidal behavior Symptoms Symptoms include: Nausea Vomiting Excessive sweating Pale skin Symptoms of liver failure: Anorexia Nausea Vomiting Malaise Abdominal pain (especially in the upper right portion of the abdomen) Pale skin Excessive sweating Jaundice [nurseslabs.com]

  […] hypokalemia massive OD = metabolic acidosis stage 2 clinical symptoms abd pain/hepatic tenderness AST/ALT >1000 U/L massive overdose = met acidosis, prolonged PT, bilirubin elevation, hypoglycemia stage 3 clinical symptoms fulminant liver failure --jaundice [quizlet.com]

• Angioedema

  […] dose-dependent, primarily occurring during the initial hour of loading therapy when serum levels are highest. 3 While the most common features of anaphylactoid reactions are rash, urticaria, flushing, chills, and fever 4 ; more serious reactions include angioedema [calsprogram.org]

  […] activated charcoal; however, later treatment does not include charcoal unless a second toxin was ingested. 47 Intravenous administration of NAC over a 10-hour period (rapidly) is associated with a higher frequency of allergic and anaphylactoid reactions (angioedema [pediatrics.aappublications.org]

  These reactions range from mild to severe symptoms and include rash, nausea, vomiting, angioedema, tachycardia, bronchospasm, hypotension, and death (Mant 1984; Bailey 1998; Schmidt 2001; Kao 2003). [cochranelibrary.com]

A thorough preliminary physical examination to check for vital changes such as skin color, abdominal pain, blood pressure and body temperature is done. In addition, blood work is carried out to measure the levels of serum acetaminophen in the blood. Liver function tests are also required to assess the functioning of the organ.

If tests reveal a deteriorated liver function, then blood clotting factor would also be tested. This is so because, the blood takes more than longer time to clot if the liver is damaged. Serum phosphate determination may be able to prognosticate the APAP toxicity, a serum level of 1.2 mmol/L measured in 48 to 96 hours from intake is considered sensitive and specific in predicting mortality rate [7].

Acetaminophen overdose can have serious consequences. Treatment should be initiated as soon as possible to avoid irreversible damages. The following are the methods employed for treating acetaminophen overdose:

• Activated charcoal is a method that causes the individual to vomit to release out the acetaminophen from the body.
• Gastric lavage involves pumping the stomach to remove excess of acetaminophen.
• Emetics are medications to induce vomiting in individuals for moving out the drug.
• Acetylcysteine acts as an antidote which helps in preventing the harmful effects of drug overdose [10]. In case, when the body has already digested the drug, then acetylcysteine is administered to reverse the effects and prevent the body from the harmful effects.
• Cimetidine is also administered in certain cases to reduce the effect of acetaminophen overdose.

The prognosis of the condition is favorable if it is treated within 8 hours of overdose. Failure to do so can cause acute liver failure following death of the individual within some days.

Complications

Failure to initiate rapid treatment within the first few hours of overdose can cause subsequent development of complications. Liver injury is the most common complication of acetaminophen overdose. Excessive intake of acetaminophen may trigger rare and fatal allergic cutaneous reactions like Steven-Johnson’s syndrome [5] and acute generalized exanthematous pustulosis [6].

Acetaminophen is widely available and it is a compound that can be found in many medications [1]. It may so happen that patients unknowingly ingest different medications with the same compound which can eventually lead to an overdose. In teenagers and young adults however; acetaminophen overdose is usually intentional in nature and is widely associated with suicidal ideations in these age groups [2].

Individuals suffering from severe and intolerable pain often have a tendency to take more medications than the recommended dose. Such a practice can also lead to an overdose.

Acetaminophen overdose is a common occurrence that can affect both adults and children. It is considered to be one of the most common cases of drug poisoning across the globe. Statistical reports revealed that liver injury due to acetaminophen overdose was one of the major factors during the period 1998 to 2003 in the US.

According to the reports published by the Center for Disease Control and Prevention, the year 2007 witnessed about 1600 cases of liver failure associated with acetaminophen overdose. With such high prevalence rates and associated morbidity and mortality, preventive steps to avoid acetaminophen overdose should be adopted.

Acetaminophen is prescribed for treatment of mild fever and pain. When this drug is taken in doses more than the recommended levels, development of subsequent liver injury and failure can take place [3]. Small doses of acetaminophen can easily be metabolized in the liver and removed from the body through urine. However, when higher doses are ingested, there is saturation and the liver cannot function the normal way.

The toxic metabolites bind with liver proteins leading to cellular injury. Due to high doses, the liver is unable to excrete the drug before it binds to the protein. Such sequence of events paves way for development of liver injury. There are cases of acetaminophen toxicity associated with normal dose intake but was taken concurrently with alcohol causing a similar form of liver injury to overdose [4].

The various ways of preventing acetaminophen overdose include the following:

• It is necessary to carefully read the labels of medications to avoid consumption of more acetaminophen [8]. Recent USFDA regulations have limit the content of acetaminophen preparation to 325mg per capsule or tablet preparation to prevent hepatoxicity [9].
• Individuals are advised to take correct doses of medicines and at the correct time. Maintaining appropriate intervals between doses prevents overdose.
• Acetaminophen should not be taken for many days together. For treating pain, this drug should not be continued for more than 10 days. In case of fever, the drug can be continued for 3 days and not more.

Acetaminophen overdose is defined as excessive ingestion of the drug within a period of 8 hours. Acetaminophen is also known as paracetamol or APAP and is a drug prescribed for its pain relieving properties.

An overdose occurs when, either accidentally or intentionally, someone consumes more than the recommended dose of the drug within a short span of time. Such an activity is hazardous and has deleterious effect on the health of the concerned individual. Ingestion of about 7.5 to 10 grams of acetaminophen within 8 hours can lead to liver toxicity.

Definition

Ingestion of more than 7.5 to 10 grams acetaminophen in 8 hours causes overdose. If timely treatment is not initiated, it can lead to liver failure and subsequent coma and death. Acetaminophen overdose can be incidental or accidental in nature. Individuals are advised to carefully read labels before they take medications.

Cause

Acetaminophen overdose can occur due to ingestion of several medications containing the same compound. Also, if for quick relief individuals take more than the recommended dose then overdose can occur.

Symptoms

Symptoms of acetaminophen overdose include fever, weakness, irritability, abdominal pain, vomiting, and nausea, blood in urine, change in skin color, coma, confusion and even death.

Diagnosis

Diagnosis of acetaminophen overdoes includes physical examination for determining the changes in the vital signs such as color of the skin, blood pressure and body temperature. Blood tests are done to analyze the levels of acetaminophen in the blood. In addition, liver function test is also carried out. Prothrombin time and INR rates are also done to evaluate the blood clotting factor. With a deteriorated liver functioning, blood clotting ability is greatly affected.

Treatment

Treatment of acetaminophen overdose is geared towards removal of the drug from the body. Medications are given to induce vomiting through which the drug can be eliminated from the body. In addition, antidotes are also given to reduce the toxic effect due to drug overdose.

1. Acetaminophen toxicity in children. Pediatrics. Oct 2001; 108(4):1020-4.
2. Penna A, Buchanan N. Paracetamol poisoning in children and hepatotoxicity. Br J Clin Pharmacol. Aug 1991; 32(2):143-9.
3. Department of Health and Human Services; Food and Drug Administration. Organ-Specific Warnings; Internal Analgesic, Antipyretic, and Antirheumatic Drug Products for Over-the-Counter Human Use; Final Monograph. Federal Register. April 29, 2009; 74:19385-409.
4. FDA. Acetaminophen Prescription Combination Drug Products with more than 325 mg: FDA Statement - Recommendation to Discontinue Prescribing and Dispensing. U.S. Food and Drug Administration.
5. FDA. FDA Drug Safety Communication: FDA warns of rare but serious skin reactions with the pain reliever/fever reducer acetaminophen. US Food and Drug Administration.
6. Lowes R. Acetaminophen Poses Risk for Rare but Fatal Skin Reactions. Medscape Medical News. Aug 1 2013; Accessed Aug 13 2013.
7. Schmidt LE, Dalhoff K. Serum phosphate is an early predictor of outcome in severe acetaminophen-induced hepatotoxicity. Hepatology. Sep 2002; 36(3):659-65.
8. US Food and Drug Administration. Organ-specific warnings: internal analgesic, antipyretic, and antirheumatic drug products for over-the-counter human use. Federal Register. 2009 Apr 29; 74(81). 
9. US Food and Drug Administration. Acetaminophen information.
10. Whyte IM, Francis B, Dawson AH. Safety and efficacy of intravenous N-acetylcysteine for acetaminophen overdose: analysis of the Hunter Area Toxicology Service (HATS) database. Curr Med Res Opin. Oct 2007; 23(10):2359-68.