Treatment
[edit] Initial measures
The initial treatment for uncomplicated paracetamol overdose,
similar to any other overdose, is gastrointestinal decontamination.
In addition, the antidote, acetylcysteine plays an important role.
Paracetamol absorption from the gastrointestinal tract is complete
within 2 hours under normal circumstances, so decontamination is
most helpful if performed within this timeframe. Absorption may be
somewhat slowed when it is ingested with food. There is
considerable room for physician judgement regarding
gastrointestinal decontamination, activated carbon administration
is the most commonly used procedure, however, gastric lavage may
also be considered if the amount ingested is potentially life
threatening and the procedure can be performed within 60 minutes of
ingestion.[20] Syrup of ipecac has no role in paracetamol overdose
because the vomiting it induces delays the effective administration
of activated carbon and oral acetylcysteine.
Activated carbon adsorbs paracetamol, reducing its gastrointestinal
absorption. Administering activated carbon also poses less risk of
aspiration than gastric lavage. Previously there was reluctance to
give activated carbon in paracetamol overdose, because of concern
that it may also absorb acetylcysteine. Studies have shown that no
more than 39% of an oral acetylcysteine is absorbed when they are
administered together.[21] Other studies have shown that activated
carbon seems to be beneficial to the clinical outcome. It appears
the most benefit from activated carbon is gained if it is given
with 2 hours of ingestion.[22] However, administering activated
carbon later than this can be considered in patients who may have
delayed gastric emptying due to co-ingested drugs or following
ingestion of sustained or delayed release paracetamol preparations.
Activated carbon should also be administered if co-ingested drugs
warrant decontamination. There are conflicting
recommendations[21][23] regarding whether to change the dosing of
oral acetylcysteine after the administration of activated carbon,
and even whether the dosing of acetylcysteine needs to be altered
at all.
[edit] Acetylcysteine
Acetylcysteine (also called N-Acetylcysteine or NAC) works to
reduce paracetamol toxicity by supplying sulfhydryl groups (mainly
in the form of glutathione, of which it is a precursor) to react
with the toxic NAPQI metabolite so that it does not damage cells
and can be safely excreted. (NAC can be bought as a dietary
supplement in the United States.)
If the patient presents less than 8 hours after paracetamol
overdose, then acetylcysteine significantly reduces the risk of
serious hepatotoxicity. If NAC is started more than 8 hours after
ingestion, there is a sharp decline in its effectiveness because
the cascade of toxic events in the liver has already begun and the
risk of acute hepatic necrosis and death increases dramatically.
Although acetylcysteine is most effective if given early, it still
has beneficial effects if given as late as 48 hours after
ingestion.[24] In clinical practice, if the patient presents more
than 8 hours after the paracetamol overdose, then activated carbon
is probably not useful, and acetylcysteine is started immediately.
In earlier presentations the doctor can give carbon as soon as the
patient arrives, start giving acetylcysteine, and wait for the
paracetamol level from the laboratory.
In United States practice, intravenous (IV) and oral administration
are considered to be equally effective. However, IV is the only
recommended route in Australasian and British practice.
Oral acetylcysteine is given as a 140 mg/kg loading dose followed
by 70 mg/kg every 4 hours for 17 more doses. Oral acetylcysteine
may be poorly tolerated due to its unpleasant taste, odor, and its
tendency to cause nausea and vomiting. It can be diluted to a 5%
solution, from its marketed 10% or 20% solutions, to improve
palatability. Where oral acetylcysteine is required, the inhalation
formulation of acetylcysteine (Mucomyst) is often given orally. The
respiratory formulation can also be diluted and filter sterilized
by a hospital pharmacist for IV use, however this is an uncommon
practice. If repeat doses of carbon are indicated because of
another ingested drug, then subsequent doses of carbon and
acetylcysteine should be staggered every two hours.
Intravenous acetylcysteine (Parvolex/Acetadote) is used as a
continuous intravenous infusion over 20 hours (total dose 300
mg/kg). Recommended administration involves infusion of a 150 mg/kg
loading dose over 15 minutes, followed by 50 mg/kg infusion over 4
hours; the last 100 mg/kg are infused over the remaining 16 hours
of the protocol. Intravenous acetylcysteine has the advantage of
shortening hospital stay, increasing both doctor and patient
convenience, and it allows administration of activated carbon to
reduce absorption of both the paracetamol and any co-ingested drugs
without concerns about interference with oral
acetylcysteine.[25]
Baseline laboratory studies include bilirubin, AST, ALT, and
prothrombin time (with INR). Studies are repeated at least daily.
Once it has been determined that a potentially toxic overdose has
occurred, acetylcysteine is continued for the entire regimen, even
after the paracetamol level becomes undetectable in the blood. If
hepatic failure develops, acetylcysteine should be continued beyond
the standard doses until hepatic function improves or until the
patient has a liver transplant.
[edit] Prognosis
The mortality rate from paracetamol overdose increases 2 days after
the ingestion, reaches a maximum on day 4, and then gradually
decreases. Patients with a poor prognosis are usually identified
for likely liver transplantation. Acidemia is the most important
single indicator of probable mortality and the need for
transplantation. A mortality rate of 95% without transplant was
reported in patients who had a documented pH of < 7.30. Other
indicators of poor prognosis include renal insufficiency, grade 3
or worse hepatic encephalopathy, a markedly elevated prothrombin
time, or a rise in prothrombin time from day 3 to day 4. One study
has shown that a factor V level less than 10% of normal indicated a
poor prognosis (91% mortality) while a ratio of factor VIII to
factor V of less than 30 indicated a good prognosis (100%
survival).
That was from Wiki, I have no idea what it is saying, can anyone
smart explain? 
