Question

    Acetaminophen Overdose

    Acetaminophen Overdose emerges due to the following process: Drugs.

    Presentation

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

    Liver, Gall & Pancreas
    Jaundice
    • Jaundice is a serious condition in infants and requires prompt medical attention.[livestrong.com]
    • 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]
    • The systemic symptoms of stage I reappear in conjunction with jaundice, confusion (hepatic encephalopathy), a marked elevation in hepatic enzymes, hyperammonemia, and a bleeding diathesis.[quizlet.com]
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  • Entire body system
    Gastric Lavage
    • Activated charcoal, gastric lavage, and ipecacuanha are able to reduce the absorption of paracetamol, but the clinical benefit is unclear.[cochrane.org]
    • Gastric lavage is also called having your stomach pumped.[drugs.com]
    • In our patient's case, she was already vomiting so gastric lavage was not performed.[hawaii.edu]
    • Gastric lavage: Gastric lavage is also called having your stomach pumped.[allinahealth.org]
    Malnutrition
    • 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]
    • 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]
    • Predicting Overdose Outcomes The 53 patients whose records were analyzed for the new study varied in alcohol use, malnutrition status and whether they took too much acetaminophen in a suicide attempt, an accidental single overdose or a chronic, multiple-day[archive.unews.utah.edu]
    • Malnutrition, concomitant illness, long-term ethanol use, genetic predisposition, and coingestion with substances metabolized by the liver have all been proposed as potentiating factors for acetaminophen-associated hepatocellular injury. 14 , 15 Thus,[archopht.jamanetwork.com]
    • […] blood clotting problems , confusion [1] Complications Kidney failure , pancreatitis , low blood sugar , lactic acidosis . [1] Usual onset After 24 hours (toxicity) [2] Causes Paracetamol (acetaminophen) usually 7 g [3] [2] Risk factors Alcoholism , malnutrition[en.wikipedia.org]
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  • gastrointestinal
    Nausea
    • In the first 24 hours, they may feel stomach pain and nausea.[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.[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]
    Persistent Vomiting
    • […] administration include a high-risk patient who meets the following conditions 2,3 : Has intractable vomiting and thus cannot tolerate oral NAC but delay in treatment will result in a decrease in the efficacy of NAC (eg, beyond 10 hours post ingestion); Has persistent[calsprogram.org]
    Vomiting
    • Emetics are medications to induce vomiting in individuals for moving out the drug.[symptoma.com]
    • She has vomited 3-4 times at home.[hawaii.edu]
    • 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]
    • If vomiting occurs, an antiemetic can be used; if vomiting occurs within 1 h of a dose, the dose is repeated.[merckmanuals.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]
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  • 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].

    Pathology

    Biopsy
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  • Laboratory

    Serum
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  • 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].

    Complications

    Acute Kidney Failure
    • In some cases, acute kidney failure may be the primary clinical manifestation of toxicity.[en.wikipedia.org]
    Acute Liver Failure
    • Participants agreed to follow-up at one and two years following acute liver failure.[uofmhealth.org]
    • Acetaminophen (Tylenol) overdose is the most common cause of acute liver failure in the United States.[health.ucsd.edu]
    • Acetaminophen toxicity is one of the most common causes of poisoning and is the most common cause of acute liver failure.[percodanabusehelp.com]
    • He goes on to explain that people who go into acute liver failure from an acetaminophen overdose experience three phases.[sharecare.com]
    • The drug, also found in over-the-counter cold formulas and pain-relieving prescription favorites Vicodin and Percocet, is the most common cause of acute liver failure in the U.S.[articles.latimes.com]
    Hepatic Encephalopathy
    • The systemic symptoms of stage I reappear in conjunction with jaundice, confusion (hepatic encephalopathy), a marked elevation in hepatic enzymes, hyperammonemia, and a bleeding diathesis.[quizlet.com]
    • Secondary outcome measures were clinical symptoms, (eg, hepatic encephalopathy, fulminant hepatic failure), hepatotoxicity, adverse events, and plasma paracetamol concentration.[cochrane.org]
    • Hepatotoxicity was defined as any increase in aspartate transaminase (AST) concentration, severe hepatotoxicity as an AST concentration greater than 1,000 IU per L, and hepatic failure as hepa-totoxicity with hepatic encephalopathy.[aafp.org]
    • Read about hepatic encephalopathy.[forums.studentdoctor.net]
    • These criteria utilize the serum prothrombin time, serum creatinine, pH and presence or absence of hepatic encephalopathy.[caribbean.scielo.org]
    Hyperglycemia
    • Previous reported cases have been associated with hyperglycemia, hypothermia, and elevated venous oxygen saturation.[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]
    Hypoglycemia
    • Signs of severe hepatotoxicity include plasma ALT and AST levels that often exceed 10,000 IU/L, prolongation of the PT or INR, hypoglycemia, lactic acidosis, and a total bilirubin concentration above 4.0 mg/dL (primarily indirect).[quizlet.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]
    • Poor prognostic indicators at 24 to 48 h postingestion include all of the following: pH 7.3 after adequate resuscitation INR 3 Serum creatinine 2.6 Hepatic encephalopathy grade III (confusion and somnolence) or grade IV (stupor and coma) Hypoglycemia[merckmanuals.com]
    • […] report decreased urinary output (oliguria) Phase 3: Hepatic phase 72-96 h after ingestion Patients have continued nausea and vomiting, abdominal pain, and a tender hepatic edge Hepatic necrosis and dysfunction may manifest as jaundice, coagulopathy, hypoglycemia[emedicine.medscape.com]
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  • 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.

    Sex distribution
    Age distribution

    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.

    Self-assessment

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    References

    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. 

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