Originally Posted by IPCS INCHEM
9.3 Course, prognosis, cause of death
The course of amanitin intoxication has 3 chronological 3 phases:
a) A latent phase of approximately 6 - 24 hours (mean 12.3
hours), rarely extending to 48 hours.
b) A gastrointestinal phase with abdominal pain, vomiting and
diarrhoea causing dehydration, hypovolaemia, electrolyte and
acid-base disorders. This phase usually lasts 2-3 days.
c) An hepatic phase which begins 36 - 48 hours after ingestion.
The pre-icteric phase can only be detected by an increase in
serum transaminases. Hepatitis becomes clinically evident with
the onset of jaundice on the 3rd -4th day after ingestion. In
severe intoxications, patients develop fulminant hepatitis with
hepatic coma, bleeding and anuria. When liver damage is
reversible, patients usually make a slow and steady recovery. In
fatal cases death occurs within 6 - 16 days (mean 8 days).
Prognosis: An analysis of the literature shows that the factors
most likely to indicate a poor prognosis in Amanita hepatitis are
peak prothrombin time > 100 sec; factor V < 10%; lactic
acidosis; gastrointestinal bleeding; and age < 12 years. Other
criteria, such as the duration of the latency period; the peak
serum concentration of aminotransferases; and amanitin analysis
are not useful for prognosis. Orthotopic liver transplantation
should be considered in patients with poor prognosis criteria.
In a study of 205 amanita intoxications, the gastrointestinal
syndrome was present in 199 patients and hepatitis in 198; 52
patients developed hepatic coma and the overall mortality was
22.4% (Floersheim et al, 1982)
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
In the gastrointestinal phase, vomiting and diarrhoea can
produce severe fluid losses resulting in hypovolaemic shock
with tachycardia and a fall in central venous pressure.
Functional reversible renal failure often accompanies
hypovolaemic shock secondary to gastrointestinal fluid loss.
When shock occurs in the hepatitic phase, it is mainly due
to haemorrhage secondary to severe coagulation disorders.
Cardiovascular collapse also accompanies severe hepatic
failure in the terminal phase.
9.4.2 Respiratory
Respiration is usually normal but hyperventilation
accompanies fulminant hepatitis. Respiratory failure with
hyperventilation or apnoea may occur in patients presenting
with hepatic coma and has a poor prognosis.
9.4.3 Neurological
9.4.3.1 CNS
Neurologic symptoms are related to hepatic
encephalopathy which usually occurs 5 - 6 days after
ingestion. Somnolence and confusion are the first
signs, and coma usually follows. Convulsions may be
observed in hepatic coma.
In severe hepatic failure, coma may also be due to
hypoglycaemia secondary to disordered glucose
metabolism.
9.4.3.2 Peripheral nervous system.
No data available.
9.4.3.3 Autonomic nervous system
No data available.
9.4.3.4 Skeletal and smooth muscle
No data available.
9.4.4 Gastrointestinal
Gastrointestinal symptoms appear after a latent period of 6
- 24 hours (mean 12.3 hours). In a study of 205 Amanita
intoxications, gastrointestinal symptoms were present in 199
patients (Floersheim et al, 1982).
a) Nausea, vomiting, colic.
There is a sudden onset of colicky abdominal pain rapidly
followed by nausea, frequent vomiting and diarrhoea.
b) Diarrhoea
In most cases, diarrhoea is severe, watery and cholera-like.
In the absence of fluid replacement, diarrhoea rapidly
induces dehydration, haemoconcentration and hypovolaemic
shock. Diarrhoea may persist for 2 - 4 days.
9.4.5 Hepatic
Clinical signs of hepatocellular damage usually develop on
the 3rd to 4th day after ingestion. Clinical presentation
may only include a mild jaundice and a mild hepatomegaly.
In severe cases, hepatitis follows a fulminant course with
marked jaundice and hepatic coma and may be accompanied by
renal failure and cardiovascular collapse. In fatal cases,
death occurs within 6 - 16 days (mean 8 days).
9.4.6 Urinary
9.4.6.1 Renal
Two types of renal failure may be observed. During the
gastrointestinal phase a functional renal failure is
frequent. It is associated with hypovolaemia and is
secondary to fluid loss and to hypoperfusion of the
kidneys. It may improve if dehydration and
hypovolaemia are corrected aggressively.
Anuria and renal failure may occur during the third
phase of poisoning together with severe hepatitis,
hepatic coma and haemorrhage.
Serious kidney complications may be avoided by
administration of fluids (Constantino et al, 1978,
Vesconi et al, 1985). A direct nephrotoxic effect of
amatoxins has not been proven in human intoxication.
9.4.6.2 Others
No data available.
9.4.7 Endocrine and reproductive systems
No data available.
9.4.8 Dermatologic
Mild jaundice with icteric sclerae is present in the hepatic
phase.
9.4.9 Eyes, ear, nose, throat: local effects
Eyes:Scleral icterus occurs.
Nose:Nasal haemorrhage may occur in patients with
coagulation disorders secondary to severe
hepatocellular damage. If intubation is necessary, the
nasal route should be avoided because it may induce
severe local haemorrhage.
9.4.10 Haematological
Severe hepatocellular damage may result in severe
haemorrhage.
Usually the earliest indication of coagulopathy is
persistent bleeding from IV puncture sites (Bivins et al,
1985). Other bleeding, epistaxis and gastrointestinal
haemorrhage may occur.
These are due to marked coagulation defects secondary to
impaired synthesis of clotting factors. This indicates a
poor prognosis. (Floersheim, 1987).
9.4.11 Immunologic
No data available.
9.4.12 Metabolic
9.4.12.1 Acid based disturbances
In the gastrointestinal phase, metabolic acidosis may
occur as the result of bicarbonate loss in diarrhoea;
in later stages, acidosis may be due to hepatic
failure.
9.4.12.2 Fluid and electrolyte disturbances
Dehydration and hypovolaemia
The gastrointestinal syndrome often results in marked
dehydration and hypovolaemia with haemoconcentration
and functional renal failure.
Electrolyte disturbances
Hypokalaemia is particularly common in the
gastrointestinal phase.
9.4.12.3 Others
Glucose
Glucose metabolism is often disturbed in severe hepatic
failure. Spontaneous hypoglycaemia results from
impaired glycogenolysis and gluconeogenesis (Bivins et
al, 1985).
Hepatic enzymes
Elevated serum transaminase, LDH and serum bilirubin
are the first and best indicators of liver damage and
should be monitored throughout the course of the
illness. Hepatic enzymes usually reach a peak after 60
- 72 hours and then decrease. Enzyme levels may be
relatively low in massive liver necrosis (Bivins et al,
1985).
Coagulation parameters
Coagulation disorders indicate hepatic insufficiency.
Levels of clotting factors synthesized by the liver,
such as fibrinogen and prothrombin, may be decreased.
A prothrombin level below 10 per cent indicates a poor
prognosis (Floersheim 1987)
9.4.13 Allergic reactions
No data available.
9.4.14 Other clinical effects
Amatoxin does not affect temperature regulation directly but
temperature disorder may occur in severe hepatic failure
with encephalopathy.
9.4.15 Special risks: pregnancy, breast feeding, enzyme
deficiency
Pregnancy: Kauffmann et al, (1978) reported a Amanita
phalloides poisoning in a 25 year old woman at 9 weeks
gestation. The patient developed a toxic hepatitis
(transaminase 1800 U/l). After life threatening maternal
illness was overcome, a therapeutic abortion was carried out
at 12 weeks gestation. Histologic examination of the foetal
liver showed cellular damage related to amanitin toxicity.
Amatoxins therefore cross the placenta barrier in
concentrations sufficient to affect the foetus.
Breast-feeding: Because amatoxins are excreted in breast
milk, nursing mothers who have ingested Amanita, whether
they are symptomatic or not, should be told to stop nursing
until it is determined whether or not they have been
poisoned (Bivins et al, 1985).
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