Transcript Case 3.1 - rEMERGs

Apap cases
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
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?
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?
When would you expect the
aminotransferases to become
elevated?
• 24 - 48 hours post ingestion
• How does NAC work?
How does NAC work?
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
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 30-60 minutes should prevent most
anaphylactoid reactions.
How should our patient be
treated?
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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?
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 Nacetylcysteine.
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, Nacetylcysteine can be stopped and the
patient can be medically cleared.
When would you continue Nacetylcysteine longer than 20
hours?
• If AST or ALT elevated (but INR normal) at
the completion of 20 hours of Nacetylcysteine, 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. 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?
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. 1100 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?
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 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?
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?
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INR > 5 at anytime.
Metabolic acidosis (pH <7.35 or CO2 <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 Nacetylcysteine and on May 14 his INR
was 1.16.
• Will this patient have any chronic liver
damage from his acetaminophen
overdose?
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?
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?
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?
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
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Cyanide
The Land Lady
Roald Dahl
Tampered Tylenol was laced with cyanide.