Hepatic Failure/GI/Endocrine Emergencies
| (b) | Many poison centers may extend therapy beyond the recommended course if there is |
|---|
a detectable acetaminophen concentration or if ALT concentrations continue to remain
elevated at the end of therapy, especially if therapy was initiated more than 8 hours after
ingestion and baseline acetaminophen concentrations were greater than 300 mcg/mL
when extrapolated on the RumackβMatthew nomogram.
| (c) | Recent studies have evaluated alternative dosing strategies for patients with massive |
|---|
overdoses, including doubling the last bag (i.e., providing 200 mg/kg over 16 hours).
Massive overdoses are considered ingestions with initial acetaminophen concentrations
greater than 300 mcg/mL when extrapolated on the RumackβMatthew nomogram, or a
single ingestion greater than 30 g; doubling the last bag has been associated with reduced
hepatotoxicity. However, these strategies must be further evaluated.
| (d) | Therapy may continue until the signs and symptoms of encephalopathy or coagulopathy |
|---|
resolve or until the patient receives a liver transplant. The 2023 ACG ALF guidelines note
that duration of NAC treatment for APAP-induced ALF should be βindividualized based on
| (e) | Additional information on treatment of acetaminophen-induced ALF can be found in the |
|---|
Toxicology chapter.
Route
Dose
Oral
Loading dose: 140 mg/kg Γ 1 dose
Maintenance dose: 70 mg/kg every 4 hr Γ 17 doses (72 hr total)
IV
150 mg/kg (max 15 g) over 60 min, followed by
50 mg/kg (max 5 g) over 4 hr, followed by 100 mg/kg (max 10 g) over 16 hr (21 hr total)
IV = intravenous.
NAI-ALF
Acetylcysteine may improve oxidative stress in NAI-ALF by acting as a free radical scavenger.
In addition, acetylcysteine may improve both hepatic and systemic perfusion through its
vasodilatory effects.
ii.
A multicenter randomized trial compared intravenous acetylcysteine with placebo for 72 hours
(see Table 5) for treatment of NAI-ALF. Randomized patients were stratified according to
coma grade, with most patients having a low-grade encephalopathy. There was no difference
in the primary outcome of overall survival at 3 weeks between acetylcysteine and placebo;
however, the transplant-free survival rate significantly increased with the use of acetylcysteine
(40% vs. 27%, p=0.04).
| (a) | The increase in transplant-free survival with acetylcysteine was mainly confined to the |
|---|
subgroup of patients with encephalopathy grade I and grade II (52% vs. 30% with placebo,
p=0.01).
| (b) | When outcomes were compared on the basis of each etiology of NAI-ALF, patients with |
|---|
DILI and hepatitis B virus had more improvement in overall survival and transplant-free
survival from acetylcysteine compared with placebo than with other causes.
iii.
Intravenous acetylcysteine has also been studied for the treatment of NAI-ALF as a loading
dose followed by a continuous infusion of 150 mg/kg over 24 hours until resolution of
coagulopathy (INR less than 1.3). This strategy increased transplant-free survival compared
with a historical cohort (96.4% vs. 23.3%, p<0.01); however, the strategy needs to be further
evaluated.