Presentation
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
Entire Body System
- Fever
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. [symptoma.com]
How to Prevent Acetaminophen Overdose It is advised to not take this medicine for pain or low grade fever, unless the pain or fever is quite high and with the approval of a doctor. [newhealthguide.org]
Do not take acetaminophen for more than 3 days to treat a fever, unless your healthcare provider tells you to. Your pain or fever may need to be treated another way if it lasts longer than a few days. [drugs.com]
Definition Acetaminophen is a medicine used to relieve pain and reduce fever. [healthofchildren.com]
- Anorexia
Corrected calcium = serum calcium + 0.8 (4 - serum albumin) Recognize the clinical signs and symptoms of acetaminophen toxicity in: 1. stage I 1. can be asymptomatic or have: N/V diaphoresis malaise, anorexia pallor normal ALT/AST until 12hrs Recognize [quizlet.com]
Early nonspecific signs that may be present in the first 24 hours include anorexia, nausea, vomiting, or vague abdominal pain. [online.epocrates.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]
Findings: Symptoms and Signs Anorexia Nausea and Vomiting Lethargy Elevated Liver Function Test s to Jaundice and liver failure Pallor X. [fpnotebook.com]
- Gastric Lavage
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]
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]
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]
- Weakness
The role of haemodialysis is debated, in part because the evidence base is weak and the endogenous clearance of acetaminophen is high. There is also concern because the antidote acetylcysteine is also dialyzable. [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]
Presence of blood in the urine Fever, shaking, lightheadedness Severe weakness, tiredness, fainting Rapid breathing, difficulty in breathing Rapid heartbeat, continued headache Blurred vision Difficulty in staying awake, confusion Coma When to See a Doctor [newhealthguide.org]
My first symptom was debilitating nausea and weakness. Saliva was pouring from my mouth and nose, and abdominal pain was constant. I perspired profusely. The acute phase lasted about 45 minutes. [emedicinehealth.com]
Dark-colored urine or decreased urination Skin and eyes turn yellow (jaundice) If you have ignored these symptoms for a few days, you may also suffer from: Bloody urine Fever Lightheadedness and fainting Increased respiration or breathing difficulties Extreme weakness [justbelieverecovery.com]
- Swelling
Death may also occur due to brain swelling, infection, or organ failure. Phase IV (7-14 days after acetaminophen consumption) – At this point, patients either recover or die from liver failure. [schmidtandclark.com]
The patient may also experience kidney failure, bleeding disorders, and in extreme circumstances even swelling of the brain. [healthoma.com]
Anyone who develops symptoms such as a rash, swelling, or difficulty breathing after taking acetaminophen should stop taking the drug and get immediate medical attention. [healthofchildren.com]
A serious allergic reaction is rare, but signs include itching; swelling of the face, tongue and throat; rash; severe dizziness; and trouble breathing. [draxe.com]
Gastrointestinal
- 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]
If the patient vomits and is unable to retain the NAC, antiemetics may be administered. [calsprogram.org]
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]
- 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]
Nausea and vomiting are typically the initial symptoms that develop following Tylenol overdose. An infant may spit up more than usual or may be uninterested in breast-feeding or bottle-feeding due to nausea or decreased appetite. [livestrong.com]
- Abdominal Pain
Discomfort resulting from abdominal pain can cause irritability and crankiness in infants. An infant may cry or fuss more than usual and can be difficult to console. [livestrong.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]
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]
- Diarrhea
Persistent or severe diarrhea or irritability should be reported to a doctor immediately. These overdose symptoms can be indicative of alternate medical complications. [livestrong.com]
Telltale symptoms of an acetaminophen overdose may include abdominal pain, loss of appetite, convulsions, diarrhea, jaundice, and coma. [schmidtandclark.com]
Signs of acetaminophen overdose include: Abdominal pain, upset stomach, nausea, vomiting, and appetite loss Convulsions Jaundice Diarrhea Irritability Sweating Coma About the Author: James Heubi, MD James Heubi, MD, is a pediatric gastroenterologist with [blog.cincinnatichildrens.org]
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 [symptoma.com]
- Loss of Appetite
Telltale symptoms of an acetaminophen overdose may include abdominal pain, loss of appetite, convulsions, diarrhea, jaundice, and coma. [schmidtandclark.com]
Symptoms of an overdose can include: loss of appetite nausea vomiting pain in the abdomen or belly, especially in the upper right side Also seek emergency care if you notice any symptoms of an overdose, such as loss of appetite, nausea and vomiting, or [healthline.com]
There are three symptomatic phases of liver damage: nausea, vomiting, loss of appetite, and other flu-like symptoms; an inactive phase during which there is no discomfort; and the appearance of liver blood test abnormalities. [livescience.com]
The first signs of an acetaminophen overdose include loss of appetite, nausea, vomiting, stomach pain, sweating, and confusion or weakness. [drugs.com]
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 [symptoma.com]
Cardiovascular
- Hypertension
RESULTS: Baseline demographics were similar in the two groups with the exception of more hypertension in the low m-MELD group (24 vs 7%; P= .02). Time to admission was shorter in the low m-MELD group (7.9 ± 9.3 vs. 25.7 ± 29.2 hours; P= .001). [ncbi.nlm.nih.gov]
The pregnancy had been complicated by pregnancy-induced hypertension, treated with labetalol. Prior to the overdose, the baby had been well. [cmaj.ca]
Liver, Gall & Pancreas
- 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]
As a result, infants who overdose on Tylenol can develop jaundice, a symptom characterized by unusual yellowing of the skin or whites of the eyes. Jaundice is a serious condition in infants and requires prompt medical attention. [livestrong.com]
[…] post-ingestion initial symptoms go away and the pt feels better, then: RUQ pain increased ALT/AST, PT oliguria, anuria (increased BUN, Cr) hepatomegaly Recognize the clinical signs and symptoms of acetaminophen toxicity in: 1. stage III 1. 72-96hrs jaundice [quizlet.com]
- Hepatomegaly
AST until 12hrs Recognize the clinical signs and symptoms of acetaminophen toxicity in: 1. stage II 1. 24-72hrs post-ingestion initial symptoms go away and the pt feels better, then: RUQ pain increased ALT/AST, PT oliguria, anuria (increased BUN, Cr) hepatomegaly [quizlet.com]
Skin
- 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]
Neurologic
- Irritability
Discomfort resulting from abdominal pain can cause irritability and crankiness in infants. An infant may cry or fuss more than usual and can be difficult to console. [livestrong.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]
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]
Signs of acetaminophen overdose include: Abdominal pain, upset stomach, nausea, vomiting, and appetite loss Convulsions Jaundice Diarrhea Irritability Sweating Coma About the Author: James Heubi, MD James Heubi, MD, is a pediatric gastroenterologist with [blog.cincinnatichildrens.org]
- Convulsions
ADR were significantly associated with IV-NAC administration: vomiting (p = .001), flushing (p < .001), rash (p < .001), pruritus (p < .001), chest pain (p = .001), bronchospasm (p = .03), coughing (p = .01), headache (p = .001), dizziness (p < .001), convulsion [ncbi.nlm.nih.gov]
Parents or caregivers may observe that an infant appears to abnormally shake, twitch or convulse. Certain infants may also lose consciousness following Tylenol overdose. If left untreated, Tylenol overdose in infants can result in coma or death. [livestrong.com]
Signs of acetaminophen overdose include: Abdominal pain, upset stomach, nausea, vomiting, and appetite loss Convulsions Jaundice Diarrhea Irritability Sweating Coma About the Author: James Heubi, MD James Heubi, MD, is a pediatric gastroenterologist with [blog.cincinnatichildrens.org]
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 [symptoma.com]
- Seizure
Symptoms may include: Abdominal pain, upset stomach Appetite loss Coma Seizures Diarrhea Irritability Jaundice (yellow skin and whites of the eyes) Nausea, vomiting Sweating Note: Symptoms may not occur until 12 or more hours after the acetaminophen was [medlineplus.gov]
Symptoms Symptoms may include: Abdominal pain, upset stomach Appetite loss Coma Seizures Diarrhea Irritability Jaundice (yellow skin and whites of the eyes) Nausea, vomiting Sweating Note: Symptoms may not occur until 12 or more hours after the acetaminophen [mountsinai.org]
Furthermore, alcohol and certain medications such as phenobarbital, phenytoin ( Dilantin ), or carbamazepine ( Tegretol ) (anti- seizure medications) or isoniazid (INH, Nydrazid, Laniazid) - (anti- tuberculosis drug) can significantly increase the damage [medicinenet.com]
- Agitation
Estimation of agitation intensity in the GI tract in humans and dogs based on in vitro/in vivo correlation. Pharm Res 1995;12:237–43. DOI 10.1023/A:1016231010301 Google Scholar | Crossref | Medline | ISI 16. [journals.sagepub.com]
Common Side Effects of Acetaminophen Include: Constipation (infrequent or difficult to pass bowel movements) Agitation Headaches Insomnia (trouble falling asleep or staying asleep) Vomiting Complications Associated with Tylenol Tylenol is associated with [drugwatch.com]
Workup
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].
Serum
- Hypoglycemia
[…] pallor diaphoresis massive OD = lethargy/decreased consciousness 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 [quizlet.com]
All patients were treated with N-acetylcysteine and, despite the early high anion gap metabolic acidosis, none developed hepatic failure or hypoglycemia. [ncbi.nlm.nih.gov]
[…] acetaminophen overdose has 4 recognized stages: Stage Time Symptoms 1 First 24 hours Nausea, vomiting, anorexia, diaphoresis 2 24 to 48 hours RUQ tenderness, elevated transaminases 3 Day 3 to 4 Jaundice, coagulopathy, renal failure, encephalopathy, hypoglycemia [clinlabnavigator.com]
[…] play by the rules… Stage 1 — 0-24h — preclinical stage — nonspecific symptoms Stage 2 — 24-72h — onset of liver injury — N&V, RUQ pain, abnormal LFTs, lacate, Cr Stage 3 — 72-96h — maximal hepatotoxicity — liver failure, renal failure, coagulopathy, hypoglycemia [lifeinthefastlane.com]
- Hyperglycemia
A 14-yr-old boy admitted unconscious with lactic academia and hyperglycemia. Routine investigations. His initial investigations revealed hyperglycemia and lactic acidosis. [ncbi.nlm.nih.gov]
Previous reported cases have been associated with hyperglycemia, hypothermia, and elevated venous oxygen saturation. KEY TAKE-HOME POINT : Always remember to include APAP on the differential diagnosis of high-anion-gap metabolic acidosis. [thepoisonreview.com]
The basic mechanisms of these manifestations are obscure, but we speculate that mitochondrial inhibition could underlie all of these events and may result in the initial hyperglycemia that was manifested by our patient. [forums.studentdoctor.net]
Treatment
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.
Prognosis
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].
Etiology
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.
Epidemiology
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.
Pathophysiology
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].
Prevention
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.
Summary
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.
Patient Information
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.
References
- Acetaminophen toxicity in children. Pediatrics. Oct 2001; 108(4):1020-4.
- Penna A, Buchanan N. Paracetamol poisoning in children and hepatotoxicity. Br J Clin Pharmacol. Aug 1991; 32(2):143-9.
- 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.
- 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.
- 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.
- Lowes R. Acetaminophen Poses Risk for Rare but Fatal Skin Reactions. Medscape Medical News. Aug 1 2013; Accessed Aug 13 2013.
- Schmidt LE, Dalhoff K. Serum phosphate is an early predictor of outcome in severe acetaminophen-induced hepatotoxicity. Hepatology. Sep 2002; 36(3):659-65.
- 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).
- US Food and Drug Administration. Acetaminophen information.
- 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.