Presentation
In staggered ingestions or very late presenters (>24 hr after acute ingestion), obtain level but do not use nomogram for therapeutic guidance. [emergency.unboundmedicine.com]
A 64-year-old woman without medical history presented comatose after an ingestion of 208 tablets of Tylenol PM™ (APAP 500 mg and diphenhydramine 25 mg). [hindawi.com]
Most of them who present in the initial 24 hours of presentation will be asymptomatic,while a few may need treatment for the symptoms caused by the co-ingestants. [japi.org]
[…] and the symptoms at presentation Other causes of acute liver failure: alcoholic hepatitis, drug/toxin-induced hepatitis, viral hepatitis, shock liver, etc. [coreem.net]
In the first (n = 160) [8], 26 patients (16%) presented with staggered ingestion (20 presented within 24 h of ingestion). Nine received NAC and only three developed hepatotoxicity (all three presented more than 24 h after ingestion). [ccforum.biomedcentral.com]
Entire Body System
- Intravenous Administration
Persistent vomiting despite oral anti-emetic is an indication for intravenous administrations. [japi.org]
- Nightmare
The 72-hour oral regimen is a logistical nightmare: Oral acetylcysteine smells like rotten eggs and makes patients vomit. Patients will often refuse to continue with the regimen at some point. [emcrit.org]
Respiratoric
- Pneumonia
The patient was awake and following commands but failed extubation due to respiratory distress and pneumonia. [hindawi.com]
Supporter of FOAMed, toxicology, tropical medicine, sim and ultrasound Previous Post Pneumonia Case 003 Next Post 45 Seconds – Memoirs of an ER Doctor [litfl.com]
Gastrointestinal
- Nausea
Stage 1 2 3 4 Timing from ingestion First 24 hour Days 2-3 Days 3-4 After day 4 Sign and symptoms Loss of appetite Improvement in appetite, less nausea and vomiting. Recurrent of loss of appetite, nausea and vomiting. [myhealth.gov.my]
At toxic doses, it can cause nausea, abdominal pain, gastritis, and renal failure. In severe presentations, acidosis and electrolyte disturbances are seen. [brownemblog.com]
The majority of patients survive acetaminophen toxicity with supportive care such as intravenous fluids and anti-nausea medication, activated charcoal, if used within one hour after ingestion, and antidotal therapy, including N-acetylcysteine (Acetadote [chp.edu]
Here are some common symptoms and when they are likely to occur.5 0–24 hours—The person may experience sweating, nausea and vomiting after an overdose. [humana.com]
Toxic dose: 150–200 mg/kg, but not to exceed 8–10 g (acute) or > 4 g/day (chronic) Nausea, vomiting shortly after ingestion Hepatic necrosis evident after 24–48 h Nausea or vomiting shortly after ingestion Hepatic aminotransferase levels begin to increase [accessmedicine.mhmedical.com]
- Abdominal Pain
Stage III there is worsening liver injury and symptoms such as abdominal pain, nausea, vomiting, confusion, jaundice, and multiple organs fail. [epmonthly.com]
At toxic doses, it can cause nausea, abdominal pain, gastritis, and renal failure. In severe presentations, acidosis and electrolyte disturbances are seen. [brownemblog.com]
Case Presentation A 24-year-old obese woman presents complaining of abdominal pain, vomiting, and malaise. [acepnow.com]
Beyond 24 hours, symptoms should be evident (nausea, vomiting, abdominal pain or encephalopathy). [litfl.com]
Symptoms and side effects include: Abdominal pain Irritability Generalized weakness Loss of appetite Jaundice (yellow appearance of skin and eyes) Diarrhea Nausea Vomiting Convulsions Coma Acetaminophen Toxicity Diagnosis A doctor’s first step in diagnosing [chp.edu]
- Constipation
His symptoms began five hours prior to arrival, and are not accompanied by diarrhea, constipation, genitourinary, urologic, or musculoskeletal symptoms. He provides limited history and appears tearful. [brownemblog.com]
Liver, Gall & Pancreas
- Liver Tenderness
Clinical improvement and recovery (7–8 days) or Deterioration to multi-organ failure and death Nausea Abdominal pain Altered mental status Vomiting Liver tenderness jaundice Lethargy Table 2 : A correlation between sign and symptoms of paracetamol ingestion [myhealth.gov.my]
As stage II progresses, patients develop right upper quadrant pain, with hepatomegaly and liver tenderness. [journals.lww.com]
- Murphy's Sign
The patient is diaphoretic with mild epigastric and right upper quadrant abdominal tenderness and no rebound or guarding; Murphy sign is negative. [acepnow.com]
Workup
A high serum acetaminophen level, increased creatinine, and severely elevated liver enzymes, INR, and lactate were found on the initial workup. [dpic.org]
Workup consisted of an EKG plus typical toxicologic labs, and consultation from poison control. His EKG showed normal intervals and aVR morphology. [brownemblog.com]
Figure 4: Diagram of diagnostic workup of drug-induced liver injury (Kullak-Ublick G.A. et al., 2017 with changes of authors). [heraldopenaccess.us]
See Workup. Oral activated charcoal avidly adsorbs acetaminophen. [emedicine.medscape.com]
Treatment
Now that’s three days of delightful treatment. Add in a somewhat altered patient and that makes a miserable shift for a nurse. That’s straightforward acetaminophen toxicity treatment. [epmonthly.com]
The duration of treatment varies by route. [brownemblog.com]
2 Patients receiving IV NAC treatment Primary Outcome Measures : Duration of oral vs IV NAC treatment in hours [ Time Frame: From admission to discharge ] Secondary Outcome Measures : Overall healthcare costs associated with IV vs Oral NAC treatment [clinicaltrials.gov]
[…] individuals might develop liver injury during the treatment period also which might necessitate extension of the treatment.43 Serum acetaminophen measurement is also recommended during the end of treatment in order to guide if treatment duration needs [japi.org]
The analysis was done according to randomised treatment group, irrespective of adherence to treatment (intention to treat). [thelancet.com]
Prognosis
There are few published data on outcome and prognosis in accidental/staggered poisoning. [ccforum.biomedcentral.com]
Early Williams R. indicators of prognosis in fulminant hepatic failure.Gastroenterology. 1989; 97: 439-445 Bernal W. Donaldson N. Wyncoll D. Wendon J. [ajemjournal.com]
About 1% to 3% of patients with severe liver failure need to undergo a liver transplant as a life-saving measure.[25][26][27] In general, children less than 6 years of age have a better prognosis than adults, chiefly because of their greater capacity [ncbi.nlm.nih.gov]
In this case, the pre-mortem dosage of transaminases showed rates higher than 10x normal, which already determines a very poor prognosis. [omicsonline.org]
In patients who experience hepatic failure due to acetaminophen, the prognosis is better for full recovery than in those with hepatic failure from other causes. [cancertherapyadvisor.com]
Etiology
with resolution of symptoms and gradual normalization of liver function studies.2,5,6 Diagnosis Diagnosis of acute acetaminophen overdose relies on a detailed history and high suspicion in patients presenting with GI symptoms without another clear etiology [reliasmedia.com]
Acetaminophen directly acts on the hypothalamus producing an antipyretic effect.[4] Etiology Even though acetaminophen has a good safety profile at therapeutic levels, it can cause severe liver toxicity if taken in large amounts. [ncbi.nlm.nih.gov]
Use of substances that induce the activity of the APAP-metabolizing CYP enzymes may increase the risk of morbidity by enhancing the production of NAPQI (see Etiology). [emedicine.medscape.com]
This article reviews the etiology, signs, and symptoms of acetaminophen toxicity and the role of the pharmacist in the prevention of acetaminophen misuse. [uspharmacist.com]
Epidemiology
A perspective on the epidemiology of acetaminophen exposure and toxicity in the United States. Expert Rev Clin Pharmacol. 2014;7(3):341-8. PMID: 24678654 Bizovi KE et al. [coreem.net]
Emergency department visits for acetaminophen overdose: a Canadian population-based epidemiologic study (1997-2002). Can J Emerg Med. 2007; 9: 267-74. Sivilotti MLA, et al. Antidote removal during haemodialysis for massive acetaminophen overdose. [dpic.org]
A bibliometric analysis in the fields of preventive medicine, occupational and environmental medicine, epidemiology, and public health. BMC Public Health 2006; 6: 301. Google Scholar | Crossref | Medline | ISI 50. Alubo, SO. [journals.sagepub.com]
Toxicity develops at 7.5 g/day to 10 g/day or 140 mg/kg.[5] Epidemiology Acetaminophen toxicity is the second most common cause of liver transplantation worldwide and the most common in the US. [ncbi.nlm.nih.gov]
Pathophysiology
Reversing this pathophysiology and providing supportive care is accomplished through intramuscular epinephrine (increases systemic vascular resistance and decreases bronchoconstriction), intravenous H1/H2 blockers (decreases vasodilation and third-spacing [brownemblog.com]
Age < 5 years and acute alcohol ingestion seem to decrease susceptibility to acetaminophen toxicity.2,5 Pathophysiology Acetaminophen is quickly absorbed from the GI tract and reaches peak serum levels in 1-4 hours. [reliasmedia.com]
Pharmacological research. 2016 Jul [PubMed PMID: 26921661] [5] Ye H,Nelson LJ,Gómez Del Moral M,Martínez-Naves E,Cubero FJ, Dissecting the molecular pathophysiology of drug-induced liver injury. [statpearls.com]
Dissecting the molecular pathophysiology of drug-induced liver injury. World J. Gastroenterol. 2018 Apr 07;24(13):1373-1385. [PMC free article: PMC5889818] [PubMed: 29632419] 6. Caparrotta TM, Antoine DJ, Dear JW. [ncbi.nlm.nih.gov]
Severe hypotension seen in NAC overdose due to a vasodilatory effect and the consequent oliguria raises the issue of prerenal pathophysiology and acute renal failure. [dovepress.com]
Prevention
Many, like the case above, were potentially preventable, but the issues are complex. For National Poison Prevention Week (March 15-21, 2015), we would like to highlight acetaminophen poisoning and what pharmacists can do to help. [dpic.org]
Can prevent damage to the liver. The earlier it is given, the better the outcome will be. Prevention To help reduce your chance of acetaminophen poisoning: Follow directions for taking medicine: Read package or labels carefully. [wnyurology.com]
Indeed, NAC can prevent liver failure if given early enough. For this reason, it is absolutely necessary that acetaminophen poisoning be recognized, diagnosed, and treated as early as possible. [webmd.com]
How can you prevent acetaminophen toxicity in children? To prevent an acetaminophen overdose, follow dosage instructions carefully. Talk to your child’s provider about the right dose based on your child’s weight and age. [my.clevelandclinic.org]