Apap cases

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Apap cases
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Case 3.1

• 21 year old woman brought to the ED by her
  boyfriend. He had learned that she had ingested
  30 325mg Tylenol tablets in an attempted suicide.
  She ingested the tablets about 3 hours ago.
• She vomited once at home.
• PMH noncontributory

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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.

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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?

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Rumack-Matthew Nomogram
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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.

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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?

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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?

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When would you expect the aminotransferases to
become elevated?

• 24 - 48 hours post ingestion
• How does NAC work?

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How does NAC work?
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What is the dose of NAC and how is it
administered?

• Initial infusion 150 mg/kg in 250-500 cc of D5W
  over 30-60 minutes.
• 2nd infusion 50 mg/kg in 500-1000 cc of D5W over
  4 hours,
• 3rd infusion 100 mg/kg in 1000 cc of D5W over 16
  hours

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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?

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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
  30-60 minutes should prevent most anaphylactoid
  reactions.

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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?

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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?

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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?

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Pregnancy

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

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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?

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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.

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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).

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Case 3.2

• On May 3 (approx. 2200 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?

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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.

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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. 1100 hours he
  developed abd pain and N/V and returned to the
  ED.

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Case 3.2

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

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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.

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Case 3.2

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

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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.

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Case 3.2

• On May 5 his acetaminophen level was
  nondetectable and his AST was 22733 (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?

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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 10,000s IU/L.
• In alcoholics with acetaminophen overdoses and
  elevated aminotransferases, err on the side of
  caution and treat with IV NAC.

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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.

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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?

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When would you transfer this patient to a
hospital that could do liver transplants?

• INR gt 5 at anytime.
• Metabolic acidosis (pH lt7.35 or CO2 lt18)
• Hypoglycemia.
• Renal Failure (creatinine gt200 umol/L)
• Encephalopathy.

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What are the indications for a liver transplant?

• pH lt7.3 after adequate fluid replacement.
• Grade III or IV encephalopathy plus either
• PT gt100 seconds
• Creatinine gt 292 umol/L

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Case 3.2

• The patient was continued on IV N- acetylcysteine
  and on May 14 his INR was 1.16.
• Will this patient have any chronic liver damage
  from his acetaminophen overdose?

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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.

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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?

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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?

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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?

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Should we calculate an acetaminophen half life?

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

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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

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Tox Trivia

• Name the toxin?
• No, thank you, Billy said. The tea tasted
  faintly of bitter almonds, and he didnt much
  care for it.
• What short story it this excerpt from?
• Who is the author
• How does this relate to acetaminophen?

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Tox Trivia

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