Transcript Tylenol_overdose - Royal Columbian Hospital

Tylenol Toxicity
Kelly Kasteel
1
OBJECTIVES
• Tylenol toxicity :
a) Epidemiology
b) Dosing
c) Metabolism
d) Diagnosis
e) Treatment
f) Prognosis
2
3
Epidemiology

Tylenol- A name by many others

Most popular OTC analgesic in North America

Lay people commonly underestimate its toxicity
Acephen™ [OTC]; Apra Children's [OTC]; Aspirin Free
Anacin® Maximum Strength [OTC]; Cetafen Extra® [OTC]; Cetafen® [OTC]; Comtrex® Sore Throat Maximum
Strength [OTC]; FeverALL® [OTC]; Genapap™ Children [OTC]; Genapap™ Extra Strength [OTC]; Genapap™
Infant [OTC]; Genapap™ [OTC]; Genebs Extra Strength [OTC]; Genebs [OTC]; Infantaire [OTC]; Mapap
Children's [OTC]; Mapap Extra Strength [OTC]; Mapap Infants [OTC]; Mapap [OTC]; Nortemp Children's
[OTC]; Pain Eze [OTC]; Silapap® Children's [OTC]; Silapap® Infants [OTC]; Tycolene Maximum Strength
[OTC]; Tycolene [OTC]; Tylenol® 8 Hour [OTC]; Tylenol® Arthritis Pain [OTC]; Tylenol® Children's with Flavor
Creator [OTC]; Tylenol® Children's [OTC]; Tylenol® Extra Strength [OTC]; Tylenol® Infants [OTC]; Tylenol®
Junior [OTC]; Tylenol® [OTC]; Valorin Extra [OTC]; Valorin [OTC] .
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Epidemiology



intentional (suicidal)=unintentional (chronic)
poisonings
Tylenol is often thought to be benign, or is
a “hidden ingredient” in other remedies.
Accounts for more overdoses and overdose deaths
each year in North America than any other
pharmaceutical agent
 In 2000, it accounted for 5% of overdoses and
23% of reported fatalities.5
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Dosing



“Plain Tylenol”:
1.
Regular-strength:
325mg
2.
Extra-strength:
500mg
Pediatric syrup

1. 160 mg/5 mL –Childrens

2. 80 mg/0.8 mL -Infants
Other Tylenol formats include:
a)
tablets
b)
chew-tabs
c)
dissolvable
d)
capsules
e)
suppositories
6
Dosing

Tylenol is also available as a co-ingredient
in several combination medications:
1. Tylenol #3 (Tylenol 300 and Codeine
30mg)
2. Percocet (Tylenol 300mg and
Oxycodone 2.5/5/7.5mg)
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Dosing

Recommended Tylenol dosing is as
follows:



Adult: 325-650 mg every 4-6 hours or 1000
mg 3-4 times/day; do not exceed 4 g/day.
2.5mg in liver failure ( defined as
Peds: 10-15 mg/kg/dose every 4-6 hours as
needed; do not exceed 5 doses (80mg/kg) in
24 hours
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Acute Toxic Dosing

The minimum toxic dose for an acute
ingestion of Tylenol (ie. occurring within a
time frame of four hours) is:
a) Adults: 7.5g
b) Peds: 150mg/kg


It may be prudent to also use these levels as
the minimum acute toxic dose per 24 hours.
Ingestions occurring over a period of more
than four hours are arbitrarily termed chronic
ingestions.
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Chronic Toxic Dosing


The minimum toxic dose for chronic
ingestions of Tylenol is less well defined.
Rosen’s suggests:4
a) Adults: > 4g/d if risk factors **
> 7.5g/d if no risk factors
b) Peds: > 75 mg/kg/d if risk factors
> 150mg/kg/d if no risk
factors
 **
- Risk factors will be discussed later
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Metabolism


Immediate-release Tylenol is rapidly
absorbed in the gut, with peak serum levels
typically achieved in 30m – 2hr
Peak serum levels can be delayed…
1.
2.
3.
With sustained-release formulations.
With combination formulations.
In overdoses.
a)
b)
peak levels not being achieved for up to 4hrs following
overdoses of immediate-release Tylenol.
peaks even >4hrs following OD’s of extended-release
Tylenol.2
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Metabolism


Okay… time to make learning fun.
Who hasn’t memorized and forgotten the
pathways of Tylenol metabolism at least five
times?


Well… here’s number six.
Under normal circumstances, Tylenol is
metabolized in the following manner:
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Tylenol
Sulfation
5%
20-45%
Glucuronidation 40-65%
Oxidation
Remaining
5-15%
NAPQI
Cyt P450
Tylenol –
mercaptate
compound
Glutathione
NORMAL TYLENOL METABOLISM
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Tylenol
Sulfation
5%
20-45%
Glucuronidation 40-65%
Oxidation
Remaining
5-15%
NAPQI
Cyt P450
Tylenol –
mercaptate
compound
Glutathione
NORMAL TYLENOL METABOLISM
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Tylenol
Tylenol
SATURATED5%
SATURATED
20-45%
Sulfation
SATURATED
Glucuronidation 40-65%
Oxidation
Remaining
>>>
55-15%
15%
NAPQI
NAPQI
Cyt P450
Tylenol mercaptate
compound
Glutathione
TYLENOL METABOLISM IN OVERDOSE
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Risk Factors for Tylenol Toxicity
 An obvious corollary of the previous slide is
that anything which potentiates the action of
Cyt P450 will accelerate the production of
NAPQI.

(And vice-versa.)
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Risk Factors
Cyt P450 Potentiators (
1.
2.
Chronic alcohol consumption
Anticonvulsants:



3.

5.
Tegretol
Dilantin
Phenobarb
Anti-tuberculosis medications:

4.
NAPQI):
Rifampin
INH
Dexamethasone
St. John’s Wort
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(Not) Risk Factors
Cyt P450 Inhibitors (
Acute alcohol consumption
Macrolides
1.
2.
•
3.
4.
5.
6.
7.
NAPQI):
Erythromycin, Biaxin, Zithromax
Antifungals
Amiodarone
HIV protease-inhibitors
Cyclosporine
Grapefruit juice
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Quick note on the sauce…


As you can see, if you are going to overdose
on Tylenol, at least have the good sense to
wash it down with some Scotch.
Chronic EtOH use, on the other hand, will
(at least, theoretically) increase the risk of
sequelae in Tylenol OD:
1.
2.
Cyt P450 is potentiated.
Alcoholics tend to have low
of glutathione.
pre-existing levels
19
Quick note on the sauce…
In practice, alcoholics tend not to be at
increased risk for hepatotoxicity following an
acute overdose of Tylenol.
Practice matches theory more closely,
however, in alcoholics with chronic Tylenol
overdoses.



Even so, these pts are still unlikely to develop
toxicity if they restrict their Tylenol use to <4g/d.
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*
More Risk Factors

Anything that slows down or interferes with
sulfation and/or glucouronidation will leave
more Tylenol available for Cyt P450 processing
(and NAPQI production).
1.
2.
3.
Septra and AZT are metabolized via glucouronidation
(and may slow this pathway down for Tylenol).
Patients with Gilbert’s disease may have decreased
glucouronidation.
Elderly patients may have decreased rates of
sulfation and/or glucouronidation.
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More Risk Factors

Anything that decreases the amount of
glutathione in the body leaves less of it available
to bind to NAPQI.
1.
Chronically malnourished or acutely fasting
patients may have decreased glutathione stores.

2.
Febrile pediatric patients are especially susceptible to
falling
into the latter group.
Elderly patients can have chronically decreased
glutathione stores.
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Summary of Risk Factors
1.
2.
3.
4.
5.
6.
7.
Induced Cyt-P450
Chronic alcoholism
Acute fasting (may include febrile peds)
Chronic malnutrition
Septra or AZT use
Gilbert’s disease
Elderly patients
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Pictorial
Summary of
Risk Factors
1. Elderly patient.
2. Fallen off
wagon.
3. On INH for TB.
4. On Septra for
bladder
infection.
5. Septra is making
her vomit…
so she’s not
eating.
6. Gilbert’s disease.
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Treatment

(For reasons that I hope will later become
obvious), I will now break with tradition and
discuss treatment before diagnosis.
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Clinical Stages
• In untreated patients, there are four
clinical stages of Tylenol toxicity:
1. Stage One (0-24hrs)
• minimal clinical findings.
• may be completely asymptomatic.
• may have minor non-specific
findings such as N/V, pallor,
malaise.
• liver panel unremarkable.
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Clinical Stages
• In untreated patients, there are four
clinical stages of Tylenol toxicity:
2. Stage Two (Day 2-3)
• clinical signs of hepatotoxicity.
Most • RUQ pain, hepatomegaly,
sensitive
AST/ALT/bili/PT/lipase elevation.
• patients may also develop early
signs of renal failure or pancreatitis
during this stage.
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Clinical Stages
• In untreated patients, there are four
clinical stages of Tylenol toxicity:
2. Stage Two continued…
• From Stage 2, patients progress
either to Stage 4 (with subsequent
full recovery) or to Stage 3 (with
subsequent probable death).
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Clinical Stages
• In untreated patients, there are four
clinical stages of Tylenol toxicity:
3. Stage Three (Day 3-4)
• Fulminant hepatic failure +/- death
• Associated lactic acidosis, coagulopathy, encephalopathy; possible
pancreatitis, hypoglycemia, ARF.
• Marked elevation of liver enzymes
(with AST typically >3,000),
• Elevation of NH3, coags, lactate.
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Clinical Stages
• In untreated patients, there are four
clinical stages of Tylenol toxicity:
3. Stage Three continued…
• Stage 3 will progress to:
(a)death.
(b)if lucky, a liver transplant.
(c)if even luckier, Stage 4 and a full
recovery.
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Clinical Stages
• In untreated patients, there are four
clinical stages of Tylenol toxicity:
4. Stage Four (Day 4 - 10)
• If you do not die in Stage 3, you
arrive at Stage 4 with rapid and
complete hepatic recovery.
• Clinical recovery usually begins by
Day 4 and is complete by Day 7-10.
• Histological recovery may take up to
3 months.
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Clinical Stages
• In untreated patients, there are four
clinical stages of Tylenol toxicity:
• Summary of stages:
Days:
1.
Minimal symptoms
1
2.
Moderate symptoms
2-3
3.
Severe symptoms +/- death 3-4
4.
Complete recovery
4-10
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Treatment


The treatment for Tylenol toxicity is Nacetylcysteine, or NAC.
Early on in Tylenol toxicity, NAC:
1.
2.
3.
Acts as a glutathione precursor, increasing
glutathione stores.
Binds NAPQI directly.
Enhances the sulfation pathway.
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Treatment

Later on in Tylenol toxicity…
(when Tylenol levels are absent, but
hepatotoxicity has begun)
…NAC continues to offer benefit:
1.
2.
3.
4.
5.
It has strong antiinflammatory effects.
It has strong antioxidant effects.
It scavenges free radicals.
It modifies cytokine production.
It increases inotropy and vasodilation, thereby
improving microcirculation.
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Treatment



So how well does NAC work?
Pretty bloody well.
If NAC is initiated within 8 hours of (even a
massive) acute Tylenol overdose, the
patient:
1.
2.

Is very unlikely to suffer (even transient)
serious hepatotoxicity.
Essentially never dies from the overdose
Beyond the 8-hour point, NAC’s protective
abilities steadily diminish.
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Treatment
But NAC continues to provide significant
benefit even if initiated quite late in Tylenol
toxicity:



In a 1991 trial in the BMJ, 50 patients presenting
with Tylenol-induced fulminant liver failure were
randomized to either: (a) NAC (b) Supportive
care
NAC patients had significantly less:
1.
2.
3.
mortality (20% vs. 48%)
cerebral edema (40% vs. 68%)
need for inotropes (48% vs. 80%)
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Diagnosis
37
Diagnosis
• The diagnosis of a disease (as any
medical student will tell you) begins
with history.
• Sadly, with Tylenol toxicity, history
can sometimes be a bit of a problem.
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Diagnosis

Patients coming to
the ED with a
Tylenol overdose
dose are not, strictly
speaking, the most
reliable of
historians.
• So you really
have to rely on
something else.
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Diagnosis

As such, the diagnosis of Tylenol toxicity
rests on:
1.
2.
3.

Tylenol levels
AST/ALT (and other bloodwork) levels
The Rumack-Matthew nomogram.
The “other bloodwork” to consider drawing
in Tylenol toxicity includes:
1.
2.
PT, BUN/Cr, glucose, lipase, CK
Medication levels (eg. ASA, EtOH, etc.)
40
Cost of Diagnosis


In a 1989 study in the Annals of Emergency
Medicine, 1 in 500 patients who presented
to the ED with an overdose—but denied
Tylenol ingestion—was found to have a
potentially toxic level.5
Tintinalli estimates that the cost of drawing
500 negative Tylenol levels is less than the
cost of missing one case of Tylenol-induced
hepatic failure.5
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RumackMatthew
Nomogram
• This is the Cdn
units (umol/L)
version of the
Rumack-Matthew
nomogram.
• Therapeutic
Tylenol levels are
70-130 umol/L.
• Note that
the y-axis is
logarithmic.
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• “Tylenol levels”
on the y-axis
range from
0 – 2000.
• “Time since
ingestion” on the
x-axis ranges
from 0 – 24
hours.
• Toxicity cannot
be predicted
before 4hrs or
after 24hrs using
this nomogram.
43
• The nomogram is
based on a study
of a large number
of patients who
following an
acute OD of
immediaterelease Tylenol
were not treated
with antidote.2
• Note that there
are two diagonal
lines indicating
potential toxicity.
44
• The original
nomogram used
just one line –
the upper line.
• Following an
acute ingestion of
immediaterelease Tylenol,
no patients with
a Tylenol level
below the upper
line…
• developed severe
hepatotoxicity or
died.
45
• The U.S. FDA later
developed a
second line—the
lower line—to
offer an increased
safety margin.
• Presumably to
cover those
patients with risk
factors for Tylenol
toxicity.
46
• Americans use
the lower line as
their indicator to
treat.
• Canadians
(choosing to base
their treatment
protocols on
actual research)
use the upper
line.
47
• To use the
nomogram…
• Wait until at least
four hours after
ingestion of an
acute OD of
immediaterelease Tylenol
• (This 4hr waiting
period ensures
that serum levels
have peaked.)
• Then simply draw
and plot the
Tylenol level.
48
• N.B. It is safe to
wait for 4hrs
before drawing
the first Tylenol
level.
• This is because
the risk of Tylenol
toxicity (following
an acute OD) is
essentially zero as
long as NAC is
initiated within
8hrs of ingestion.
49
• Plot points below
the upper-line
represent:
• negligible risk
of significant
hepatotoxicity
• essentially no
risk of longterm morbidity
or mortality.
• And, thus, no
need for
treatment.
50
• Plot points above
the upper-line
represent…
1. 60% chance
of AST > 1000
2. 1% chance of
renal failure
3. 5% chance of
mortality
• And, thus, the
need for
treatment.
51
• So… draw your
level, plot your
point, start your
NAC.
• Piece of cake
right?
• Well… mayhab,
mayhab no.
52
Diagnosis
There are some potential problems with
the Rumack-Matthew nomogram.
1.
2.
3.
What about chronic or multiple ingestions?
What if the time of acute ingestion is not firmly
established?
What if the pt is lying to you?
4. What if the acute ingestion
was <4 or >24 hours ago?
5. What about sustained-release Tylenol?
53
#
Diagnosis
What about chronic or multiple ingestions?
1.

It is generally accepted that the nomogram is
not reliable in this situation.

Tylenol levels could potentially be therapeutic (or, for
that matter, undetectable) even in the face of
significant hepatotoxicity.
54
Diagnosis
2. What if the time of acute ingestion is not
firmly established?



In this instance (since the actual time of
ingestion may well be >8hrs ago), one would be
wise to draw a Tylenol level at once and initiate
NAC immediately.
This is especially true for patients who have RUQ
pain, are jaundiced, or look ill.
When the Tylenol (and other bloodwork) levels
come back, one can decide whether or not to
continue therapy.
55
Diagnosis
3. What if the pt is lying to you?
 If you have these,
then feel free to trust
all your patients and
follow the nomogram.
– If you are not quite as trusting, then draw
a Tylenol level at once and and initiate
NAC immediately.
– At least one conscientious, young (and
handsome) physician I know recommends
trusting no one.
56
Diagnosis
4. What if the ingestion was < 4 or >24 hours
ago?

As already mentioned, the nomogram is
unreliable outside of these timeframes.
a)
b)
If <4hrs from time of ingestion, Tylenol levels may
still be increasing.
If >24hrs from time of ingestion, Tylenol levels may
be undetectable, even in the face of significant
hepatotoxicity.
57
Diagnosis
5. What about sustained-release Tylenol?



There is not currently sufficient evidence to
validate (or invalidate) the nomogram for use
with sustained-release Tylenol.2
Which is not to say we don’t do use it.
In something of an “off-label” use of the
nomogram, manufacturers of sustained-release
Tylenol recommend…

“draw both a 4- and 8-hour Tylenol level, and initiate
NAC if either level is potentially toxic.”
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And now… a return to Treatment
59
Treatment


In the ED, the most difficult question to
answer is not which therapy to use (psst… use
NAC), but whether or not therapy is actually
required.
And this question will have to be answered
at least twice:
Once before the bloodwork is back.
(b) Once after the bloodwork is back.
(a)
60
Treatment

And—both times—one will need to consider
whether there is grounds for clinical
suspicion of Tylenol toxicity:
1. Hx of ingestion suggestive of toxicity.
a) acute overdose (eg. >7.5g or >150mg/kg).
b) chronic supratherapeutic use (>4g/d or
>75mg/kg).
c) chronic therapeutic use in a patient with risk
factors.
d) chronic use or overuse of sustained-release
or combined-ingredient Tylenol.
61
Treatment

And—both times—one will need to consider
whether there is grounds for clinical
suspicion of Tylenol toxicity:
2. Hx of ingestion that is not suggestive of
toxicity, but sounds like it is:
a) inconsistent.
b) incomplete.
c) a big fat lie.
62
Treatment

And—both times—one will need to consider
whether there is grounds for clinical
suspicion of Tylenol toxicity:
3. Clinical findings suspicious of Tylenol
toxicity:
a) RUQ pain
b) jaundice
c) N/V
d) lethargy and malaise
e) dehydration
63
Treatment

In summary, be clinically suspicious of
Tylenol toxicity if:
1.
2.
3.
History sounds bad.
History sounds like bullshit.
Clinical findings.
64
Treatment

So back to the original question:

When is therapy warranted?
65
Treatment before bloodwork

Before bloodwork is back, initiate NAC if:
1.
Clinical suspicion of Tylenol toxicity.



Some will argue that if the bloodwork will be back
within 8 hours of the time of ingestion, that you do
not need to initiate empiric therapy.
And, strictly speaking, this is true.
So, by all means…
66
Treatment before bloodwork

…if your patient took an acute dose of
immediate-release Tylenol at an exact and
known time, has no risk factors, and is not
potentially lying to you, then go ahead and
wait for the bloodwork to come back.
67
#
Treatment after bloodwork

After bloodwork is back, initiate and/or
continue NAC if:
1.
2.
Nomogram indicates probable toxicity.
In the setting of a unreliable nomogram* you
have:
a)
b)
clinical suspicion of toxicity and Tylenol levels are
even detectable.
clinical suspicion of toxicity with undetectable
Tylenol levels, but AST or other bloodwork is
abnormal.
68
Treatment
after
bloodwork

What if you still have clinical suspicion of toxicity
when all your bloodwork is back and it is all
completely normal?



Chances are, you worry too much.
Theoretically (although I never saw this documented
anywhere), I suppose there could be a window right
around the 24-hr mark where Tylenol levels were
undetect-able but the AST had not yet begun to rise.
I would have to have some overwhelming clinical
suspicion of Tylenol toxicity before I investigated this
scenario further.
69
Treatment Protocols

For uncomplicated Tylenol overdose, there
are two types of NAC protocols:
1.
Oral NAC



2.
A 72-hour course of therapy.
18 total doses (q4h dosing).
Total dose = 1330mg/kg of NAC.
IV NAC
1.
2.
3.
A 20-hour course of therapy.
Continuous IV infusion.
Total dose = 300mg/kg of NAC.
70
#
Treatment Protocols


For Tylenol overdose complicated by liverfailure, IV NAC is used but the infusion is
not stopped at 20 hours.
Instead, the NAC is continued until the
patient:
1.
2.
3.
Fully recovers.
Dies.
Receives a liver transplant.
71
–
–
This is the U. of A. nursing protocol for IV
NAC in uncomplicated Tylenol toxicity.
(N.B. NAC concentration = 200mg/mL)
72
Comparing Treatment Protocols
1.
Oral NAC
–
2.
method of choice in the U.S.
IV NAC
–
–
–
method of choice in Canada.
typically better tolerated.
major limitation is rate-related IV reactions
(discussed next slide), which are typically nonserious and easily controlled.
73
Comparing Treatment Protocols
• Adverse reactions with IV NAC:
1.
2.
Reported frequency is 0.2 – 21%
Reported rxns (in order of increasing
severity and decreasing frequency):





nausea/flushing/chills/fever
urticarial rash/hypotension
bronchospasm/angioedema
hemolysis
cardiovascular collapse
74
Comparing Treatment Protocols
• Adverse reactions with IV NAC:
3.
These IV-related reactions:



are dose- and rate-dependent
usually occur in the first hour of Rx
are usually easily controlled with:
a)
b)
c)
temporarily stopping the IV.
treating with antihistamines.
re-starting the IV at a (temporarily) lower-rate.
75
Comparing Treatment Protocols
• Adverse reactions with IV NAC:
4. Continuation of IV therapy is the rule in all
but life-threatening scenarios.
76
Comparing Treatment Protocols

Effectiveness of IV vs. oral NAC.
1.
2.
In an uncomplicated Tylenol overdose at <8hrs,
IV NAC is as effective as oral.
In an uncomplicated Tylenol overdose at >8hrs,
oral NAC may be superior to IV.

3.
Possibly secondary to the increased amount and duration
of oral NAC. *
In Tylenol-induced fulminant liver failure, only IV
protocols have ever been formally used and
studied.
77
Comparing
Protocolshas not been
4.
TylenolTreatment
toxicity in pregnancy
rigorously studied, but IV NAC is typically
recommended:
a)
b)
c)
d)
Fetal Tylenol toxicity is rare, but has been reported at
all stages of pregnancy.
IV NAC is safe and effective in mom.
Higher serum levels obtained with IV NAC (by
avoiding hepatic first-pass metabolism in mom) may
translate into higher serum levels in the fetus.
Exact treatment guidelines are controversial, and
require toxicological and/or obstetrical consultation.
78
Prognosis
79
Prognosis



Although AST is the most sensitive marker
for Tylenol-induced liver damage, it is a
poor prognosticator.
Two large studies (>500 patients each)1
established markers for prognosis in hepatic
failure.
Patients with poor prognostic markers can
be evaluated to see if they are eligible for
liver transplantation.
80
Prognosis

Following Tylenol-induced fulminant liver
failure, patients are eligible for liver
transplantation if:**
1.
Arterial pH < 7.30 (following fluid resuscitation)
OR
2. They have all three of the following:
a) > Grade 3 encephalopathy *
b) INR > 6
c) Cr > 300-310
** Cdn adaptation of the King’s College Hospital criteria.
81
Prognosis

Patients who meet these criteria and:
a)
Get a liver transplant…

b)
have a 66% one-year survival rate.
Do not get a liver transplant…

have a 80-90% mortality rate.
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In summary…
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Idiot’s Guide to Tylenol Toxicity
1.
2.
Patient presents with possible Tylenol
toxicity.
Unless all of the following apply * (in which
case you can wait until 4hrs post-ingestion)
immediately draw and send:
a)
b)
c)
d)
Tylenol levels
AST, PT
lytes, BUN/Cr, glucose
urine for pregnancy testing
(women only)
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Idiot’s Guide to Tylenol Toxicity
3.
4.
5.
While the bloodwork is pending, if you are
clinically suspicious of potential toxicity,
start NAC.
When bloodwork is back, if the nomogram
can be used, plot the Tylenol level and
treat as indicated.
When bloodwork is back, if the nomogram
cannot be used, rely on combination of
bloodwork and clinical suspicion to
determine need for NAC.
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Idiot’s Guide to Tylenol Toxicity
6.
If there is yet no indication to treat,
consider the possibility that Tylenol levels
may still be rising:
a)
b)

additional Tylenol may have been ingested
just before arrival at ED.
sustained-release and/or comb-ination Tylenol
may have delayed absorption kinetics in
overdose.
If these apply, draw another set of Tylenol
levels and bloodwork in 4hrs time, and use
these to guide your therapy decisions.
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Idiot’s Guide to Tylenol Toxicity
7. Patients requiring treatment with NAC will
also require:




monitoring for hepatic or renal failure.
Internal Medicine/Hepatology/ICU
consultation if hepatic failure develops
Obstetrics/Toxicology consultation if patient
is pregnant.
Psychiatric consultation if overdose
represented a suicide attempt.
87
Final Points to Discuss
1.
2.
NAC within the first 24hrs… no one dies?
True?
Charcoal? What do you think?
88
That’s all
folks…
89
90
1.
2.
3.
4.
5.
References
Burns, Ismail, et al. UpToDate Online 12.2.
“Management of acetaminophen (paracetamol)
intoxication.” April 2004.
Burns, Ismail, et al. UpToDate Online 12.2.
“Pathophysiology and diagnosis of acetaminophen
(paracetamol) intoxication.” April 2004.
Canadian Pharmacist’s Association. CPS. 2002. p175153
Marx, Hockberger, et al. Rosen’s Emergency Medicine.
5th Edition. p2069-74.
Tintinalli, Kelen, et al. Emergency Medicine. 6th Edition.
p1088-93.
91
THE END
92
Grades of Hepatic Encephalopathy *
Clinical Stage
Intellectual
functioning
Neuromuscular
function
Subclinical
Normal exam
Subtle changes only
Grade I
Decreased attention,
personality changes
Tremor, apraxia,
incoordination,
Grade II
Drowsiness, behavioural Asterixis. slowed speech,
changes
ataxia
Grade III
Confusion,
disorientation,
amnesia
Decreased reflexes,
nystagmus, clonus,
muscular rigidity
Grade IV
Stupor, coma
Dilated pupils,
decerebrate posturing
93
94