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Copyright
© 2004 Brvar et al., licensee BioMed Central Ltd. This is an Open
Access article: verbatim copying and redistribution of this article are
permitted in all media for any purpose, provided this notice is preserved
along with the article's original URL.
Crit Care. 2004; 8(1): R56–R59. Published online 2004 January 2.
Case report: fatal poisoning with Colchicum
autumnale
Miran Brvar,1 Tom Ploj,2
Gordana Kozelj,3 Martin Mozina,4 Marko
Noc,5 and Matjaz Bunc6
1Physician, Poison Control Center,
University Medical Center Ljubljana, Slovenia
2Physician, Center for Intensive Internal
Medicine, University Medical Center Ljubljana, Slovenia
3Head, Institute of Forensic Medicine,
Medical Faculty, Ljubljana, Slovenia
4Head, Poison Control Centre, University
Medical Center Ljubljana, Slovenia
5Professor, Head, Center for Intensive
Internal Medicine, University Medical Center Ljubljana, Slovenia
6Associated Professor, Institute for
Pathophysiology, Medical Faculty and Department for Cardiology, University
Medical Center Ljubljana, Slovenia
Received September 28, 2003; Revisions requested
November 18, 2003; Revised November 26, 2003; Accepted December 17,
2003.
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Introduction
Colchicum autumnale, commonly known as the autumn crocus,
contains alkaloid colchicine with antimitotic properties.
Case report
A 76-year-old man with a history of alcoholic liver disease and renal
insufficiency, who mistakenly ingested Colchicum autumnale instead
of wild garlic (Aliium ursinum), presented with nausea, vomiting
and diarrhea 12 hours after ingestion. On admission the patient had
laboratory signs of dehydration. On the second day the patient became
somnolent and developed respiratory insufficiency. The echocardiogram
showed heart dilatation with diffuse hypokinesia with positive troponin I.
The respiratory insufficiency was further deteriorated by pneumonia,
confirmed by chest X-ray and later on by autopsy. Laboratory tests also
revealed rhabdomyolysis, coagulopathy and deterioration of renal function
and hepatic function. The toxicological analysis disclosed colchicine in
the patient's urine (6 μg/l) and serum (9 μg/l) on the second day. Therapy
was supportive with hydration, vasopressors, mechanical ventilation and
antibiotics. On the third day the patient died due to asystolic cardiac
arrest.
Discussion and conclusion
Colchicine poisoning should be considered in patients with
gastroenterocolitis after a meal of wild plants. Management includes only
intensive support therapy. A more severe clinical presentation should be
expected in patients with pre-existing liver and renal diseases. The main
reasons for death are cardiovascular collapse, respiratory failure and
leukopenia with infection.
Keywords: autumn
crocus, colchicine, Colchicum autumnale, death, poisoning
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Colchicum autumnale, commonly known as the autumn crocus, wild
saffron and naked lady, contains alkaloid colchicine that is antimitotic,
blocking the mitosis by preventing DNA synthesis and tubulin
polymerization [1].
The clinical manifestations of colchicine poisoning are present in
three phases following a latent period of 4–12 hours. The first phase is
characterized by peripheral leukocytosis, gastrointestinal symptoms with
fluid losses and hypovolemic shock. During 24–72 hours, the second stage
of intoxication, life-threatening complications occur such as heart
failure, arrhythmias, renal failure, hepatic injury, respiratory distress,
coagulopathies, bone marrow depression and neuromuscular involvement. This
second phase can last for 5–7 days and is followed by the third phase,
characterized by leukocytosis and alopecia [2,3].
When ingested, colchicine is rapidly absorbed from the gastrointestinal
tract and is primarily metabolized by the liver in a first-order process
[4].
There is significant biliary excretion and enterohepatic recirculation [5,6].
Renal excretion is responsible for only about 20% of unchanged colchicine
elimination, although this fraction may be increased in the presence of
liver disease [7].
Colchicine has been responsible for numerous intoxications and deaths.
Colchicine is used in the management of acute gouty arthritis, and a
suicidal colchicine tablet overdose is the most common cause of colchicine
poisoning [8,9].
Accidental poisoning with Colchicum autumnale is very rare.
Searching Medline we found only four case reports of accidental poisoning
with Colchicum autumnale, and in none of them were blood colchicine
concentrations measured [10-12].
We report accidental lethal Colchicum autumnale poisoning where
blood colchicine levels were obtained.
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In spring 2003, a 76-year-old man ate two whole plants regarded as wild
garlic (Aliium ursinum). He believed wild garlic to be healthy for
his alcoholic liver disease. He also had a history of chronic renal
insufficiency and arterial hypertension, which he treated with verapamil
and trandalopril. Two hours after the ingestion, he started complaining of
nausea. Repeated vomiting and watery diarrhea appeared 4–5 hours after
ingestion. Twelve hours later the man arrived at the Emergency Department.
He brought with him the remaining plant that he had not yet eaten (Fig. 1).
The plant was identified as a poisonous Colchicum autumnale by the
toxicologist. The patient was treated with gastric lavage and 30 g oral
activated charcoal and was transferred to the intensive care unit.
On arrival at the intensive care unit, the patient complained of
diarrhea and abdominal pain. His vital signs were a Glasgow coma scale of
15, a tympanic temperature of 37.1°C, a respiratory rate of 22 counts/min,
a pulse of 122 counts/min and a blood pressure of 125/80 mmHg in the
supine position. The patient had clinical signs of dehydration and a
tender abdomen on palpation. The remaining physical examination was
unremarkable. The patient's laboratory test results are presented in Table
1.
The electrocardiogram showed a sinus tachycardia, and the chest X-ray was
normal. Abdominal ultrasound revealed hepatic steatosis. During day 1 the
patient had only gastrointestinal symptoms and was treated with 3000 ml
normal saline and repeated doses of activated charcoal. He was given 200
mmol sodium bicarbonate to treat lactic metabolic acidosis.
On day 2 the patient became somnolent. He developed acute respiratory
failure, and assisted mechanical ventilation was started. The
echocardiogram revealed heart dilatation with an ejection fraction of less
than 30%. The electrocardiogram showed only diffuse nonspecific ST
changes, yet with positive troponin I values indicating myocardial
necrosis (Table 1).
On day 3 the patient developed a high-grade fever and became
hypotensive and anuric despite hydration and noradrenaline infusion.
Abdominal peristaltic sound could not be detected and abdominal X-ray
showed a dilated intestine. Bilateral infiltrates appeared on the chest
X-rays. Antibiotic cefuroxime was started. Blood cultures remained
negative. Laboratory tests also revealed rhabdomyolysis, coagulopathy and
deterioration of metabolic acidosis, renal function and hepatic function
(Table 1).
Profuse bleeding from the nose appeared and fresh frozen plasma and
platelets were given. At the end of day 3 the patient went into asystolic
cardiac arrest and cardiopulmonary resuscitation was unsuccessful.
Subsequent toxicology analysis by gas chromatography coupled to mass
spectrometry showed colchicine in the patient gastric lavage, urine and
serum samples, which were stored in light-protected containers (Table 1)
[13].
An autopsy showed a dilatated heart with a transversal diameter of the
left ventricle of around 65 mm, pulmonary edema, bilateral
bronchopneumonia, liver and kidney necrosis, hypocellular bone marrow with
diserythopoiesis, dismyeloiesis and dismegacaryopoiesis.
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The presented patient mistakenly ingested autumn crocus instead of wild
garlic, whose leaves are used as a spice or medical plant. Autumn crocus
and wild garlic are quite similar, especially their leaves, and
unfortunately they grow in the same areas at the same time [11].
We can only speculate about the colchicine amount ingested by the
patient. The remaining plant that the patient brought to the Emergency
Department weighed around 5 g. The colchicine content of autumn crocus is
0.1–0.6% [14].
The total colchicine dose ingested by the patient could be calculated as
follows: 2 (plants) × 5 g (weight of the plant) × 0.1–0.6% (content of
colchicine in the plant)/73 kg (patient's weight). The estimated
colchicine dose ingested by the patient was between 0.14 mg/kg (10 mg) and
0.82 mg/kg (60 mg).
According to published data, gastrointestinal symptoms are usually
observed at doses less than 0.5 mg/kg and doses greater than 0.8 mg/kg are
almost invariably fatal [14,15].
Everything from mild gastroenterocolitis to multiorgan failure followed by
death could therefore be expected in our patient. Serum colchicine levels
were three to six times more than the upper therapeutic level on the
second and third days [16].
We can only speculate about the highest colchicine concentration because
the colchicine blood half-life is very unpredictable, reported to be
between 20 min [1]
and 19 hours [17].
We can assume that the colchicine elimination and the blood half-life
in our patient were prolonged because the patient had alcoholic liver
disease, which reduces the hepatic colchicine metabolism and excretion
through the bile system. The patient's liver function was further worsened
by colchicine poisoning and later by the evolving shock. An excretion of
colchicine could be reduced by verapamil, which is an inhibitor of
P-glycoprotein, a protein responsible for colchicine transport from the
hepatocyte into bile [9].
A compensatory increase of colchicine excretion through the kidneys was
observed in cases of hepatic failure [7].
In our case the compensatory excretion was not possible since the
patient's chronic renal insufficiency was additionally deteriorated by
hypotension, hypoxia and rhabdomyolysis due to the colchicine effect on
muscle cells. The higher colchicine concentration on the third day
compared with on the second day observed in our patient corresponds to the
two-compartment model of colchicine kinetic coupled with impaired
elimination in the second phase, mainly due to liver and renal
insufficiency.
On the first day the intoxication caused gastroenterocolitis and
dehydration. Dehydration in combination with impaired cardiac function
resulted in tissue hypoperfusion with lactic acid metabolic acidosis. The
respiratory insufficiency was deteriorated by bilateral pneumonia,
confirmed on autopsy. Acute heart failure was probably the result of a
direct toxic effect of colchicine on myocardial cells [8,18,19].
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Colchicine poisoning should be considered in patients with
gastroenterocolitis after a wild plant meal. Blood and urine colchicine
determination is useful for diagnostics in doubtful cases. Management
includes early intensive support measures despite a relatively mild
clinical picture at presentation. Specific therapy such as colchicine
antibodies is reported in some case reports as well as in animal studies
but it is not yet commercially available [20,21].
A more severe clinical presentation should expected in patients with
pre-existing liver and renal diseases. The main reasons for death are
cardiovascular collapse, respiratory failure and leukopenia with
infection. Hepatic and renal dysfunction as well as certain drugs could
worsen the prognosis of poisoning with colchicine.
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• In patients with gastroenterocolitis after a wild plants meal,
especially when wild garlic is mentioned, we should always consider
poisoning with autumn crocus
• Prognosis of colchicine poisoning is worse in patients with
pre-existing liver and renal diseases
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AST, aspartate aminotransferase; ALT, alanine aminotransferase; LDH,
lactate dehydrogenase; CK, creatine kinase.
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[Full Text]
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Figure
1
Colchicum
autumnale (Emergency
Department). |
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Table
1
Laboratory data after
Colchicum autumnale
ingestion | |
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