Acetaminophen: Where is it Found? And How to Handle Too Much of It!


A 14-year-old girl with a history of suicidal behavior presents to a pediatric emergency department with polysubstance ingestion.  Over the last two days she has ingested variable amounts of lorazepam, alcohol, and DayQuil™ (acetaminophen, dextromethorphan, and phenylephrine).  She drank an unknown quantity of DayQuil™ the day prior and admits to drinking an entire bottle on the day of presentation.  The patient denies any current symptoms.

Vital signs:  T 97.9 F, BP 133/83, HR 114, RR 20, SpO2 100%

On examination, she is in no acute distress.  Her neurologic examination is non-focal with a Glasgow Coma Scale of 15.  Her abdomen is benign.  She has linear scars to the left forearm from self-injurious behavior.  She is cooperative, nonchalant about her ingestion, describes her mood as “numb”, and has a flat affect. 

Her laboratory analyses reveal an acetaminophen level of 65 mcg/mL.  Liver function tests are unremarkable, INR is 1.0, and ethanol is zero.  All other diagnostics are unremarkable.  Treatment is initiated, and she is admitted to Pediatrics for acetaminophen overdose.  


Acetaminophen, commonly referred to internationally as paracetamol, is one of the most widely used analgesics and antipyretics.  It is a major component of many over-the-counter and prescription medications (Table 1).  Each year, approximately 30,000 patients are hospitalized in the United States for acetaminophen toxicity, with half of overdoses thought to be intentional. (1)  Intentional pediatric ingestions typically occur in adolescents while unintentional ingestions are more common among younger children. (2)  The therapeutic dose in children is 15 mg/kg  every four to six hours.  The minimum toxic dose for an acute ingestion is 150 mg/kg. (3,4)  In chronic overdose, the minimum toxic threshold is 150-175 mg/kg over two to four days. (3,5)  

Table 1: Common Medications Containing Acetaminophen
Alka-Seltzer Plus ® NORCO® Sudafed®
Dayquil® Nyquil® Theraflu®
Excedrin® Paracetamol Tylenol® Brand Products
Hydrocet® Percocet® Vicks®
Lortab® Robitussin® Vicodin®
Mucinex® Singlet®

The clinical manifestations of acute acetaminophen poisoning in children are nonspecific.  Initially, patients may be asymptomatic or have mild symptoms such as nausea and vomiting.  Liver injury can occur after approximately 24 hours and manifest as right upper quadrant pain or tenderness, vomiting, jaundice, and elevations in transaminases and prothrombin time.  At peak liver injury, patients can present with signs of fulminant liver failure such as hepatic encephalopathy, systemic inflammatory response system, hypotension, and death. (6)

All patients in whom acetaminophen toxicity is suspected should have a serum acetaminophen concentration drawn.  In patient with a single acute ingestion, the time of ingestion should be established, as a serum acetaminophen concentration at four hours post-ingestion will determine the need for antidotal therapy with N-acetylcysteine (NAC).  The four-hour concentration should be plotted against the treatment nomogram, and concentrations in the probable hepatic toxicity range should be treated with NAC. (4,6,7)

Figure        SEQ Figure \* ARABIC     1      . Treatment Nomogram for Acetaminophen Toxicity, Reproduced from Rumack et. al 1975 (      ADDIN EN.CITE
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Figure 1. Treatment Nomogram for Acetaminophen Toxicity, Reproduced from Rumack et. al 1975 (7)

In chronic ingestions, the treatment nomogram cannot be used.  Laboratory testing for serum acetaminophen concentration and liver function should be obtained for any at-risk patient.  Patients with evidence of liver injury (AST greater than two times normal or greater than 120 IUL or those with serum acetaminophen levels greater than 30 mcg/mL should have antidotal therapy initiated. (5,6)

Gastric decontamination with activated charcoal is recommended in all pediatric patients who present within four hours of acetaminophen ingestion.  Contraindications include gastrointestinal obstruction or any altered mental status in which airway protection is a concern.  Endotracheal intubation should not be performed solely for the purpose of giving activated charcoal.  Activated charcoal has not been shown to reduce acetaminophen absorption when given greater than four hours after ingestion and is not recommended in this time frame.  Activated charcoal is given as a single dose of 1 g/kg by mouth (maximum 50 g). (8,9) 

Once the need for N-acetylcysteine antidotal therapy is determined, it should be given as soon as possible.  When given within 8 hours of ingestion, the mortality rate approaches 0; however, NAC may be beneficial up to 24 hours after ingestion.  NAC should be given intravenously (IV) if available; however, providers should be aware that IV NAC can cause severe anaphylactoid reactions.  Preparations should be made for immediate interventions if anaphylaxis occurs, and patients should be monitored closely during the initial 30 minutes of the infusion. (6,10)  Providers should also be aware that prothrombin time and INR can be artificially elevated by NAC, which can obscure signs of worsening liver function. (11) 

A well-established protocol for IV NAC dosing involves a 21-hour administration procedure detailed below.  Repeat acetaminophen levels, liver function tests, and INR should be repeated 9 hours into the protocol. (12,13)

Loading dose of 150 mg/kg IV (maximum 15,000 mg) in 200 mL dextrose 5% in water (D5W) infused over 60 minutes

Followed by

First maintenance dose of 50 mg/kg IV (maximum 5,000 mg) in 500 ml D5W infused over 4 hours

Followed by

Second maintenance dose of 100 mg/kg IV (maximum 10,000 mg) in 1000 mL D5W infused over 16 hours

Poor prognostic indicators for liver function include the King’s College Criteria.  Patients with acidosis with pH < 7.3 or patients with the combination of prothrombin time > 100 seconds and creatinine > 3.3 mg/dL and hepatic encephalopathy grade III – IV (marked confusion or coma) are considered high risk for fulminant liver failure and should be transferred to a liver transplant center. (14)


Given that the patient had an elevated acetaminophen level greater than 30 mcg/mL with multiple ingestions over the last 48 hours, she was treated with N-acetylcysteine.   Labs were rechecked at 19 hours after initiation of NAC.  Liver function tests and INR were stable.  Repeat acetaminophen level was < 10 mcg/mL.  She was ultimately discharged after Psychiatric evaluation with a home safety plan and outpatient Psychiatry follow up.

Faculty Reviewer: Dr. Jane Preotle


1.         Blieden M, Paramore LC, Shah D, Ben-Joseph R. A perspective on the epidemiology of acetaminophen exposure and toxicity in the United States. Expert Rev Clin Pharmacol. 2014;7(3):341-348.

2.            Myers WC, Otto TA, Harris E, Diaco D, Moreno A. Acetaminophen overdose as a suicidal gesture: a survey of adolescents' knowledge of its potential for toxicity. J Am Acad Child Adolesc Psychiatry. 1992;31(4):686-690.

3.            Kanabar DJ. A clinical and safety review of paracetamol and ibuprofen in children. Inflammopharmacology. 2017;25(1):1-9.

4.            Lewis RK, Paloucek FP. Assessment and treatment of acetaminophen overdose. Clin Pharm. 1991;10(10):765-774.

5.            Sztajnkrycer MJ, Bond GR. Chronic acetaminophen overdosing in children: risk assessment and management. Curr Opin Pediatr. 2001;13(2):177-182.

6.            Walls RM, Hockberger RS, Gausche-Hill M. Rosen's emergency medicine : concepts and clinical practice. In: Ninth edition. ed. Philadelphia, PA: Elsevier,; 2018: https://login.revproxy.brown.edu/login?url=https://www.clinicalkey.com/dura/browse/bookChapter/3-s2.0-C20141019850 Full text available from ClinicalKey Flex.

7.            Rumack BH, Matthew H. Acetaminophen poisoning and toxicity. Pediatrics. 1975;55(6):871-876.

8.            Chiew AL, Gluud C, Brok J, Buckley NA. Interventions for paracetamol (acetaminophen) overdose. Cochrane Database Syst Rev. 2018;2:CD003328.

9.            Spiller HA, Krenzelok EP, Grande GA, Safir EF, Diamond JJ. A prospective evaluation of the effect of activated charcoal before oral N-acetylcysteine in acetaminophen overdose. Ann Emerg Med. 1994;23(3):519-523.

10.          Bateman DN, Dear JW, Thanacoody HK, et al. Reduction of adverse effects from intravenous acetylcysteine treatment for paracetamol poisoning: a randomised controlled trial. Lancet. 2014;383(9918):697-704.

11.          Pizon AF, Jang DH, Wang HE. The in vitro effect of N-acetylcysteine on prothrombin time in plasma samples from healthy subjects. Acad Emerg Med. 2011;18(4):351-354.

12.          Prescott LF, Park J, Ballantyne A, Adriaenssens P, Proudfoot AT. Treatment of paracetamol (acetaminophen) poisoning with N-acetylcysteine. Lancet. 1977;2(8035):432-434.

13.          Yarema MC, Johnson DW, Berlin RJ, et al. Comparison of the 20-hour intravenous and 72-hour oral acetylcysteine protocols for the treatment of acute acetaminophen poisoning. Ann Emerg Med. 2009;54(4):606-614.

14.          O'Grady JG, Alexander GJ, Hayllar KM, Williams R. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology. 1989;97(2):439-445.

The Poor Man's Tox Screen: ECG Findings in the Acute Overdose


In the middle of a busy ED shift the tech runs up to you with an ECG. Just prior to signing the top “No STEMI” you think: “wait, why do the QRS complexes look like that?”

Figure 1 EKG.png

You walk back to triage with the tech to see a 86 year old male patient who looks unwell. Dry mucus membranes, mumbling to himself and not making sense, not responding to your questions, febrile, diaphoretic. You know something is wrong, and a quick review of his nursing home paper work gives you the answer: digoxin toxicity.

Figuring out what medication is causing problem for an altered patient can be challenging for any physician. Luckily, there are some classic ECG changes that will help clue to into what a patient may have overdosed on.

Beta Blocker

Beta blockers (such as metoprolol, propranolol, carvedilol) interfere with catecholamine effect on beta adrenergic receptors (principally Beta-1 on heart muscle cells) leading to a decreased heart rate and contractility (Yates & Manini 2012). This leads to low heart rate and blood pressure, as well as an increased probability of sinus bradycardia on ECG.

There are a few main-stays of treatment, all of which try to counteract the drugs activity at the cell. High dose insulin therapy (1U/kg/hr) with high dose glucose (0.5g/kg/hr) is thought by some to be first line for beta blocker overdose (Nelson et al. 2016). Hypoglycemia is coming in these patients, so make sure that highly concentrated (≥5% dextrose solutions) glucose is given before the insulin. If this fails to correct the hypotension, beta-selective pressers such as dobutamine and isoproterenol may help, but carry the risk of paroxysmal hypotension due to the high doses that are often required (Nelson et al. 2016). Glucagon is the classic first line treatment for beta blocker overdose, but has high rates of vomiting and requires large doses, so most hospitals will exhaust their supply before the beta blocker has time to wear off (Nelson et al. 2016). Additionally, phosphodiesterase inhibitors (inamrinone, milrinone, enoximone) can help prevent cAMP breakdown and thereby increase calcium activity within the cell to increase frequency and strength of contract (Nelson et al. 2016). Vasopressin (Holger et al. 2007), levosimendan (Archan & Toller 2008), pyruvate (Hermann et al. 2004), and fat emulsion are also possible treatment options, but only have animal trials or case reports to support their use, so it is unclear if these actually work.

Calcium channel blocker

Calcium channel blockers (such as amlodipine, nifedipine, diltiazem, verapamil) have similar effects to beta blockers (lower heart rate), but calcium channel also usually block sodium channels, causing conduction delays and QRS widening. This key difference may clue you to a calcium channel blocker overdose in a bradycardia patient.

Common treatment for both beta blockers are calcium channel blockers include high dose insulin and glucose, pressors, glucagon, and phosphodiesterase inhibitors. Calcium channel blockers toxicity can also be treated with calcium itself (3mg/kg/min of CaCl2) (Reikeras et al. 1985)

Sodium Channel Blockers

EKG Na Blocker.jpg

Sodium channels are responsible for depolarization of myocytes in the atria and ventricles, so blockade of these channels will lead to prolong depolarization and widen the QRS complex (Nelson et al. 2016). There is also a classic ECG finding of a prominent r-wave and a rightward axis of the terminal deflection of the r-wave that is seen in lead aVR of a 12-lead ECG.

This finding is a result of sodium channel blocker’s preference for blocking the right bundle of the bundle of Hiss (Yates & Manini 2012). Drugs that block this channel include lidocaine, procainamide, and flecainide.

Overdose treatment for sodium channel blockade may vary slightly depending upon the specific xenobiotic that is causing toxicity. In general, a prolonged QRS from a drug known to cause sodium channel blockade is treated with sodium bicarbonate at a rate of 1-2meq/kg as an initial bolus, followed by a drop of 150 met in 1L D5W at twice maintenance. Keep the ECG attached while doing this so a quick ECG can be done to assess for narrowing of QRS. Any overdose with a QRS longer than 100ms (Nelson et al. 2016) should be treated because of the risk of arrhythmia and death (Boehnert & Lovejoy 1985).

Potassium Channel Blockers

Potassium channels mediate cardiac repolarization, so cause lengthening of the QT interval on ECG (Barrett et al. 2016). This QT prolongation is thought to increase the risk of developing a polymorphic wide complex tachycardia known as Torsades de Pointes (Kurita et al. 1992). Many drugs can have this affect, though few use this effect therapeutically. Some examples include anti-nausea medication, anti-psychotic medication, macrolide and fluoroquinolone antibiotics, and antihistamines.

The mainstay of treatment for most potassium channel blocker xenobiotic overdoses is observation and symptomatic care. While there are not many specific treatments known for potassium channel blockade, IV magnesium (2mg) is used for treatment of prevention of Torsade’s de Pointes (Brady 2016). Electrical cardioversion and overdrive pacing are also treatment options for unstable patient in Torsades (Brady 2016).

Na/K/ATPase Blockers

Digoxin and other cardiac glycoside plants exert both therapeutic and toxic effects by blocking the action of Na/K/ATPase pump. By increasing the intracellular concentration of calcium, contractions of the heart are stronger and occur at a faster rate (Nelson et al. 2016). All this extra calcium causes makes the gives the heart cells a lower activation energy, and makes they more prone to random contraction. Blocking this pump also causes AV nodal blockade by lowering the gradient for calcium influx and thus AV nodal depolarization. These combined effects lead to the classic ECG findings of digoxin toxicity: increased automaticity with block and rhythms such as bi-directional VT (Nelson et al. 2016), atrial flutter with ventricular bradycardia, and the “scooped out” t-wave (the QRS terminates into a depressed and down-sloping ST segment with a short QT interval) known as Salvador Dali’s mustache (Ma et al. 2001).

Image caption: Life in the Fast Lane: Digoxin Effect. https://i0.wp.com/lifeinthefastlane.com/wp-content/uploads/2012/01/Digoxin-reverse-tick-salvador-dali-moustache.jpg?ssl=1

Image caption: Life in the Fast Lane: Digoxin Effect. https://i0.wp.com/lifeinthefastlane.com/wp-content/uploads/2012/01/Digoxin-reverse-tick-salvador-dali-moustache.jpg?ssl=1

Treatment includes digoxin-specific antibody fragment (DSFab) (acute toxicity dose = (mg ingested / 0.5mg/vial * 80% bioavailability; chronic toxicity dose = (serum digoxin concentration in ng/L) x (weight in kg) ÷ 100), usually 10-20 vials for acute poison and 3-6 vials for chronic poisoning in adults, 1-2 vials in children). This antidote is effective for cardiac glycosides other than digoxin (such as oleander) (Nelson et al. 2016). Atropine, phenytoin, and lidocaine have also been used, but are often not needed due to DSFab efficacy (Nelson et al. 2016).

Xenobiotic ECG Findings ECG Image Physiology Treatment
Beta-blocker (e.g. propranolol, labetalol) Sinus bradycardia Blockage of cardiac beta receptors Glucagon, high dose insulin and glucose, Pressors
Ca2+ Channel Blocker (e.g. diltiazem, verapamil) Sinus bradycardia, wide QRS Prolongation of phase 0 of nodal action potential, slowing rate of depolarization and thus heart rate High dose insulin, Pressors, glucagon, and phosphodiesterase inhibitors, calcium
Na+ Channel Blocker (e.g. TCA, local anesthetics) Wide QRS, negative deflection of terminal R wave in aVR Prolongation of phase 0 of myocyte action potential, prolonging depolarization phase of cardiac myocytes Sodium bicarbonate to pH <7.55 if QRS > than 100ms, pressors, lidocaine
K+ Channel Blocker (e.g. antipsychotics) Long QT Prolongation of phase 3 of action potential, prolonging time for repolarization Magnesium to treat or prevent Torsades de pointes
Na/K/ATPase Blocker (e.g. cardiac glycoside, digoxin) Biphasic QRS, Increased automaticity with AV block Increased calcium in cardiac myocytes increasing sensitivity to multiple signals and increasing automaticity Digoxin Immune Fab

Table 1: Summary of xenobiotic effects and associated ECG findings. 

These ECG tracings were use with the permission of Dr. Mike Cadogan, and additional images, summary, and description of ECG changes seen in overdose can be seen on his website www.lifeinthefastlane.com.

Faculty Reviewer: Dr. Jason Hack


Archan S, Toller W. “Levosimendan: current status and future prospect.” Current Opinions in Anesthesiology. 21:78-84. 2008.

Barrett K, Barman S, Boitano S, Brooks H. Ganong’s Review of Medical Physiology, 25th Edition. 2016

Boehnert MT, Lovejoy FH Jr. “Value of the QRS duration verses the serum drug level in predicting seizures and ventricular arrhythmias after an acute overdose of tricyclic antidepressant.” NEJM. 313:474-479. 1985.

Brady WJ, Laughrey TS, Ghaemmaghami CA. Cardiac Rhythm Disturbances. In: Tintinalli JE, Stapczynski J, Ma O, Yealy DM, Meckler GD, Cline DM. eds.Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e. New York, NY: McGraw-Hill; 2016. 

Graudins, A., Lee, H. M., and Druda, D. (2016) Calcium channel antagonist and beta-blocker overdose: antidotes and adjunct therapies. Br J Clin Pharmacol, 81: 453–461.

Hermann HP, Arp J, Pieske B, et. al. “Improved systolic and diastolic myocardial function with intracoronary pyruvate in patients with congestive heart failure.” Cardiovascular Drugs and Therapies. 15:405-411. 2004.

Holger JS, Engebreten KM, Fritzlar SJ, Patten LC, Harris CR, Flottemesch TJ. “Insulin vs vasopressin and epinephrine to treat beta-blocker toxicity.” Clinical Toxicology. 45:396-401. 2007.

Holstege C, Eldridge D, Rowden A. “ECG Manifestations: The Poisoned Patient.” Emergency Medicine Clinics of North America. 24:159-177. 2006.

Kurita T, Ohe T, Marui N, Aihara N, et al. “Bradycardia-induced abnormal QT prolongation in patients with complete atrioventricular block with torsades de pointes.” American Journal of Cardiology. 69(6):628-33. 1992.

Ma G, Brady W, Pollack M, Chan T. “Electrocardiographic manifestations: Digitalis toxicity.” Journal of Emergency Medicine. 20:145-152. 2001.

Nelson L, Lewin N, Howland M, Hoffman R, Goldfrank L, Flomenbaum N. Goldfrank’s Toxicologic Emergencies. 9th Edition. McGraw-Hill Companies Inc. 2011.

Reikeras O, Gunnes P, Sorlie D, Ekroth R, Jorde R, Mjos OD. Metabolic effects of high doses of insulin during acute left ventricular failure in dogs. European Heart Journal. 6:451-457. 1985.

Image Credit

Images Courtesy of Life in the Fast Lane blog and are used with permission: www.lifeinthefastlane.com