2.0 ANCC/AACN CONTACT HOURS acetaminoManaging acute phen Here’s how to gauge your patient’s risk of potentially fatal liver damage and how to intervene appropriately. BY DEBORAH H. SMITH, RN, CHCRM, CSPI, BSN, MA 58 Nursing2007, Volume 37, Number 1 www.nursing2007.com o phentoxicity ACETAMINOPHEN is a safe and 8 hours of an overdose is key to job loss and took 30 500-mg acet- effective antipyretic analgesic reducing hepatic injury and pre- aminophen tablets (15 grams) when used correctly. In excessive venting death.1 But acetamino- about 3 hours ago. Ms. Stewart amounts, however, it can cause phen toxicity can be challenging vomited twice at home and saw a kidney damage, irreversible liver to recognize at first for various few pill fragments in the emesis. damage, and death. reasons, including delayed onset She called 911 after she started to Sold under more than 50 brand of symptoms and an inaccurate vomit. She says she hasn’t taken names and found in more than patient history. any other medication or sub- 200 drug combinations, acet- In this article, I’ll use a case stances, except for her daily aminophen is one of the most study to outline an effective strat- 10 mg of loratadine for seasonal common drugs involved in over- egy for accurately assessing an allergic rhinitis. She has no doses reported to the American adult with acute acetaminophen known drug or food allergies. Association of Poison Control overdose and managing her care. Ms. Stewart’s physical exam is Centers (AAPCC).1-3 In 2004, the unremarkable. Her vital signs are: AAPCC reported 419 deaths that Overdose emergency BP, 122/82; pulse, 112; respira- involved an analgesic.4 Of these, Nadine Stewart, 29, arrives at the tions, 18; and temperature, 67 involved acetaminophen emergency department (ED) by 99.4o F (37.4o C). She weighs alone, 43 were related to acet- ambulance. She’s pale and com- 128 pounds (58 kg). aminophen plus at least one other plains of intermittent episodes of The paramedics established substance, and 108 were associat- nausea after an intentional over- intravenous (I.V.) access in Ms. ed with acetaminophen in a com- dose of acetaminophen at home. Stewart’s left arm, and she’s bination product, usually an opi- Awake and oriented to person, receiving 0.9% sodium chloride oid.4 place, and time, she tells you that solution at 75 mL/hour. The ED Prompt treatment within she was depressed about her recent physician orders 4 mg of I.V. www.nursing2007.com Nursing2007, January 59 ondansetron to treat Ms. Stewart’s How much is too much? nausea and vomiting and orders The maximum recommended dosage of acetaminophen is 4 grams/day for the following lab work: a chem- short-term use in adults. (Patients with liver problems shouldn’t take acet- istry screen, liver function panel, aminophen or other over-the-counter analgesics without first consulting their pri- urine drug screen, pregnancy test, mary care provider.) and acetaminophen level. Because American Association of Poison Control Centers guidelines indicate that the the treatment nomogram for acute toxic dose of acetaminophen for patients over age 6 is 10 grams or 200 acetaminophen overdose is based mg/kg/day, whichever is lower.8 This is equal to 31 regular-strength or 20 extra- on serum acetaminophen levels at strength tablets over 8 hours or less.1,2 4 hours or more postingestion, The Florida Poison Information Center uses the 10 grams or 200 mg/kg/day lab specimens can’t be taken for for children under age 18, but considers 7.5 grams an acute toxic dose in adults. 1,2 another hour. As long as you This equals 24 regular-strength or 15 extra-strength tablets over 8 hours or less. know that antidotal therapy will begin within 8 hours of ingestion, Rumack-Matthew nomogram you can wait until the 4-hour The lines on the nomogram indicate the risk of hepatic toxicity based on the patient’s acetaminophen level is obtained. serum acetaminophen level between 4 and 24 hours after acute ingestion. Time of ingestion is a key piece of information, and you know that the amount ingested—15 grams— 300- L is a toxic dose. (See How much is m / g 200- too much?) When you receive the c m Probable risk acetaminophen level, you can n i 100- l plot it on the nomogram to guide e Possible risk v e l ongoing treatment as I’ll discuss 50- n in detail shortly. First, though, e h Treatment should be initiated p 10- if level above the dotted line let’s look at how acetaminophen o n is metabolized and what happens i m 5- a in an overdose. t Low risk e c A All about acetaminophen 1- Taken orally in therapeutic doses, 4 8 12 16 20 24 acetaminophen is quickly and Hours after ingestion completely absorbed from the gastrointestional (GI) tract. Peak concentrations occur between 60 and 120 minutes after inges- nontoxic metabolite. drawn 4 or more hours after the tion of the immediate-release When a patient overdoses on reported time of ingestion.1,2 form, and the half-life is about 2 acetaminophen, the glucuronida- hours.1,2 Acetaminophen metabo- tion and sulfation pathways Recognizing the problem lism mainly occurs in the liver, become saturated and more acet- The initial clinical findings in with only a small amount excret- aminophen in the liver is metabo- acetaminophen toxicity often are ed unchanged in the urine.1,2 lized by the cytochrome P450 sys- vague and nonspecific, and signif- In the liver, most acetamino- tem.1,2 This depletes glutathione icant clinical evidence of hepato- phen is metabolized through the stores and lets the toxic metabo- toxicity may be delayed. This can glucuronidation and sulfation lite NAPQI accumulate, causing result in a dangerous delay in hepatic pathways; the remaining hepatic injury. Peak levels can treatment. If the patient doesn’t drug in the liver is metabolized by occur as late as 4 hours after in- receive antidotal therapy within the cytochrome P450 system into gestion of a toxic amount of acet- 8 hours of acetaminophen inges- a toxic metabolite, N-acetyl-p- aminophen.1,2 This is why the tion, it won’t be as effective in benzoquinonimine (NAPQI).1,2 Rumack-Matthew acetaminophen restoring glutathione levels and This metabolite couples with treatment nomogram begins with protecting the liver. Because of hepatic glutathione to produce a serum acetaminophen levels this, acetaminophen levels should 60 Nursing2007, Volume 37, Number 1 www.nursing2007.com be tested in all patients with sus- except for a potassium level of an I.V. form (Acetadote). pected drug overdose. 3.0 mEq/L (normal range, Administering acetylcysteine The characteristic clinical 3.5 to 5.1 mEq/L) and an acet- helps convert the toxic metabo- course of acute acetaminophen aminophen level of 240 mcg/mL. lite NAPQI into a nontoxic form. toxicity occurs in four phases.1,2 The pregnancy test is negative. The I.V. form of acetylcysteine is • Phase 1 (from 30 minutes to After adding supplemental most effective when given within 24 hours after ingestion). The pa- potassium to Ms. Stewart’s I.V. 10 hours postingestion, but can tient may experience nausea, fluids, you plot the acetamino- be used anytime up to 24 hours vomiting, anorexia, pallor, dia- phen level on the nomogram to after an acetaminophen overdose. phoresis, and malaise. However, determine toxicity. The ED physician orders oral many patients are asymptomatic NAC for Ms. Stewart, as the and appear normal. Using the nomogram antiemetic therapy was effective • Phase 2 (24 to 72 hours after Determining the time of acet- and the oral regimen is recom- ingestion). Although the GI aminophen ingestion as accurate- mended if the patient’s GI system effects become less pronounced ly as possible is key to using the is functional. The loading dose is during this phase, the patient nomogram. If you can’t accurately 140 mg/kg; the maintenance dose may complain of right upper determine the time, use the earli- is 70 mg/kg every 4 hours for an quadrant pain, indicating the est possible time of ingestion. additional 17 doses, or a total of beginning of hepatic injury. For example, suppose the time 1,330 mg/kg over 72 hours of Hepatic enzyme levels, bilirubin of ingestion is unknown or treatment.1,2 N-acetylcysteine is level, and prothrombin time (PT) uncertain, so a clinically relevant available in 10% and 20% solu- will begin to rise. The patient acetaminophen level can’t be ob- tions. Because NAC has a rotten- may develop signs and symptoms tained. If the patient has elevated egg odor, the 20% solution is of renal deterioration, such as liver function tests, treat the over- typically ordered; patients toler- decreased level of consciousness dose as potentially toxic, obtain ate the smaller volume better. If and oliguria. an acetaminophen level when your patient vomits a NAC dose • Phase 3 (72 to 96 hours after possible, and initiate antidotal within 1 hour of administration, ingestion). This phase is charac- therapy.1,2,5 If follow-up liver repeat the dose and administer terized by evidence of hepatic function tests are normal after appropriate antiemetic therapy. necrosis. Patients may experience 36 to 48 hours of treatment, anti- To administer oral NAC, dilute nausea, vomiting, jaundice, coag- dotal therapy can be discontin- it in at least a 1:3 (NAC:diluent) ulation defects, renal failure, and ued.1,2 ratio with soda, fruit juice, or hepatic encephalopathy. Ful- If the patient’s serum acet- water.