Apap cases

Case year old woman brought to the ED by her boyfriend. He had learned that she had ingested mg Tylenol tablets in an attempted suicide. She ingested the tablets about 3 hours ago. She vomited once at home. PMH: noncontributory

Case 3.1 BP 95/70; P 100; RR 20; T 37 C She appears pale and diaphoretic. She has mild epigastric tenderness on exam. She is placed on a monitor and given 50 grams of AC with sorbitol Labs including an acetaminophen level are drawn.

Case 3.1 Acetaminophen level = 1025 umol/L at 3 hours What is the Rumack-Matthew nomogram? Is a pre 4 hour acetaminophen level useful?

Rumack-Matthew Nomogram

Is a pre 4 hour post ingestion acetaminophen level useful? Low index of suspicion that acetaminophen was ingested. The level must be at least one hour post ingestion. The level must be undetectable. If any acetaminophen is detected, a repeat level at 4 hours must be done and plotted on the nomogram.

Case 3.1 Her 4 hour acetaminophen level is 1422 umol/L which plots toxic on the nomogram and IV N-acetylcysteine (NAC) is initiated. What other labs would you order now?

An ALT or AST If the ALT or AST is elevated then an INR, bilirubin, glucose and renal function should be added and checked q24h or more frequently if clinically indicated. When would you expect the aminotransferases to become elevated?

hours post ingestion How does NAC work?

What is the dose of NAC and how is it administered? Initial infusion: 150 mg/kg in cc of D5W over minutes. 2nd infusion: 50 mg/kg in cc of D5W over 4 hours, 3rd infusion: 100 mg/kg in 1000 cc of D5W over 16 hours

Case 3.1 She is started on IV NAC and 20 minutes later you are called to the bedside because she developed a rash? What are the side effects of IV NAC? How should our patient be treated?

What are the side effects of NAC? Anaphylactoid reactions can result resulting in uriticaria, bronchospasm and hypotension. Concentration and rate dependent. Most occur during the initial infusion. Diluting the initial infusion and infusing over minutes should prevent most anaphylactoid reactions.

How should our patient be treated? Temporarily stop the infusion. Diphenhydramine 50 mg IV Further dilute the infusion. Run infusion over longer period. How would your management change if this same lady presents 8 hours post ingestion?

8 hours post ingestion Draw an acetaminophen level and start IV NAC simultaneously. When the acetaminophen level returns, continuation of NAC can be determined by how it plots on the Rumack-Matthew nomogram. Why is time post ingestion to initiation of NAC so critical?

After 8 hours, the efficacy of NAC decreases with increasing time post ingestion. In two clinical studies, no patients died from hepatic failure if N-acetylcysteine was started within 8-10 hours. This same lady now states she is pregnant, how does this change your management?

Pregnancy IV NAC is not contraindicated in pregnancy and pregnant patients should be managed similarly.

Case 3.1 She completes a 20 hour course of N- acetylcysteine. Would you order any further labs now? When would you continue N-acetylcysteine longer than 20 hours?

Would you order any further labs now? At the completion of therapy in a patient with no initial elevation in aminotransferases, repeat an AST or ALT and an acetaminophen level. If both of these are normal, N- acetylcysteine can be stopped and the patient can be medically cleared.

When would you continue N- acetylcysteine longer than 20 hours? If AST or ALT elevated (but INR normal) at the completion of 20 hours of N- acetylcysteine, continue N-acetylcysteine until AST declining (repeat q12h). If AST or ALT elevated AND INR elevated at the completion of 20 hours of therapy, continue N-acetylcysteine until the INR is less than 2 (repeat q24h).

Case 3.2 On May 3 (approx hours) a 35 yo alcoholic male began to take 2-3 acetaminophen 500 mg tablets per hour because of a toothache. He continued this through the night until 0800 hours. What is the recommended therapeutic dose for acetaminophen?

Adults: 4 grams per day. Children: 75 mg/kg/day to a maximum of 4 grams per day.

Case 3.2 On May 4,the patient presented to the ED because of his toothache and was discharged home with Tylenol #3. He went home and took 3-4 Tylenol #3 at 0900 hours. At approx hours he developed abd pain and N/V and returned to the ED.

Case 3.2 His acetaminophen level was 212 umol/L and his AST was 990 IU/L. How do you interpret these numbers?

Because it is a chronic ingestion you can not plot it on the nomogram. In instances where it is a chronic ingestion or the time of ingestion is unknown, send an acetaminophen level and an AST(ALT) and if either are elevated start N-acetylcysteine.

Case 3.2 IV NAC is initiated. How does ethanol affect acetaminophen toxicity?

Ethanol and acetaminophen toxicity Chronic alcoholics are at increased risk with an acetaminophen overdose. Chronic ethanol consumption induces the cytochrome P450 pathway resulting in increased metabolism through this pathway and therefore increased NAPQI formation. Malnourishment decreases glutathione stores.

Case 3.2 On May 5 his acetaminophen level was nondetectable and his AST was (2305 hours) and his INR was 19. Is his liver failure secondary to chronic alcohol abuse or acetaminophen toxicity? How long would you continue his NAC and why?

Is his liver failure secondary to chronic alcohol abuse or acetaminophen toxicity? Aminotransferase elevation in chronic ethanol abuse rarely exceeds 1000 IU/L. It is not unusual for severe acetaminophen toxicity to have elevations in the 10,000’s IU/L. In alcoholics with acetaminophen overdoses and elevated aminotransferases, err on the side of caution and treat with IV NAC.

How long would you continue his NAC and why? Continue IV N-acetylcysteine until his INR is less than 2. N-acetylcysteine has antioxidant and free radical scavenging effects which have been shown to decrease mortality in fulminant hepatic failure.

Case 3.2 When would you transfer this patient to a hospital that could do liver transplants? What are the indications for a liver transplant?

When would you transfer this patient to a hospital that could do liver transplants? INR > 5 at anytime. Metabolic acidosis (pH <7.35 or CO 2 <18) Hypoglycemia. Renal Failure (creatinine >200 umol/L) Encephalopathy.

What are the indications for a liver transplant? pH <7.3 after adequate fluid replacement. Grade III or IV encephalopathy plus either: –PT >100 seconds –Creatinine > 292 umol/L

Case 3.2 The patient was continued on IV N- acetylcysteine and on May 14 his INR was Will this patient have any chronic liver damage from his acetaminophen overdose?

No, patients who recover from an acetaminophen overdose go onto have completely normal liver function with no chronic sequelae.

Case 3.3 An intoxicated patient presents to the ED stating that he tried to overdose on Tylenol yesterday. He is unable to give you a time on ingestion or an estimated amount. There are no family members or friends present to help clarify his history. Would you start IV NAC?

Yes, IV NAC should be started on arrival in the ED, before lab values are known. The efficacy of NAC decreases with time post ingestion. What lab tests would you order and how are they interpreted?

An acetaminophen level and an ALT or AST. Because time of ingestion is unknown, the acetaminophen level cannot be plotted on the nomogram. If either the acetaminophen level or the aminotransferases are abnormal, NAC should be continued. Should we calculate an acetaminophen half life?

No, acetaminophen half lives have not been shown to be sensitive enough to predict toxicity.

Summary Nomogram starts at 4 hours and is intended for acute overdoses. Start IV NAC within 8 hours Prolonged NAC beneficial for fulminant hepatic failure

Tox Trivia Name the toxin? “No, thank you,” Billy said. The tea tasted faintly of bitter almonds, and he didn’t much care for it. What short story it this excerpt from? Who is the author How does this relate to acetaminophen?

Tox Trivia Cyanide The Land Lady Roald Dahl Tampered Tylenol was laced with cyanide.