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CASE REPORT
Fatal Colchicine Poisoning
Elham.A. Draa1, Ali. S. Arebi,2 Safwan Alarabi3
1. Department of medicine, Facility of Medicine, University of Zawia, Libya .
2
Head of medical department, Zawia Teaching Hospital.
3
Physician, Intensive Internal Medicine.
Abstract
Colchicine poisoning is a relatively uncommon, but potentially life threatening due to the high toxicity of the
drug and ability to precipitate severe multi-organ failure in overdose. Colchicine is used primarily in the
treatment of acute attacks of gout and inflammatory diseases. We reported a case of a 18 -year-old Libyan
female who presented to the emergency department approximately 28 hour after ingesting 30 mg of colchicine
in a suicide attempt, in spite of gastric lavage, activated charcoal and supportive measures, multi-organ system
failure developed over the next two days, and patient died 3rd day after admission. Our goal was to add to
toxicological knowledge about clinical feature and treatment options of colchicine exposures were it is the 1st
fatal case reported in our hospital as colchicine poison.
Keywords: colchicine, toxicity, death, poisoning
Introduction
Colchicine is an alkaloid derived from Colchicum automnale and is used primarily in the treatment
of acute gouty arthritis.[1] The drug recently became more widely used for the treatment of many
rheumatological and nonrheumatological conditions including pseudogout, familial Mediterranean
fever amyloidosis [1], scleroderma, sarcoidosis[2], Bechet's disease [3] Paget's disease, [4]
psoriasis.[5] primary biliary cirrhosis [6] and alcoholic cirrhosis [7]. Although colchicine poisoning
is an uncommon form of drug overdose, but can lead to severe multi organ failure in overdose[8].
The amount of colchicine required for considerable morbidity and mortality varies greatly. A lethal
outcome has been reported after ingestion of only 7 mg over a 4-day period, [9]while patients have
survived after ingestions of more than 60 mg. [10] Suicide attempt with colchicine is uncommon. In
toxic doses it produces nausea and vomiting, and bone marrow suppression often leading to sepsis,
hypocalcaemia, adult respiratory distress syndrome, and direct cardio toxic effects.The most
common adverse effects of colchicine are gastrointestinal and include abdominal pain, nausea,
vomiting, and diarrhea. More rarely, it causes severe reactions such as bone marrow depression with
a plastic
anemia, agranulocytosis, and thrombocytopenia, peripheral neuritis, alopecia, and
reversible azospermia.[11] Several authors reported the occurrence of myoneuropathy and myopathy
[12], especially in association with renal impairment . rhabdomyolysis also reported.[13]. We
reported a fatal outcome following an intentional ingestion of 30 mg of colchicine in young Libyan
woman.
Case Report
A previously healthy 18-year-old Libyan female presented to the emergency department (ED) with
main complain abdominal pain, nausea and diarrhea(watery stools) and her family gave history of
suicidal attempt with anti-inflammatory drugs of her father 28hours
back
and she received
treatment as gastritis in peripheral hospital .
On admission her initial blood pressure was 110/60 mmHg, heart rate was 100beats/min, respiratory
rate was 30 breaths/min, and temperature was 37.3°C. Clinical examination was relatively good
despite epigastric pain and tachycardia no other significant findings was detected. Laboratory studies
included a complete blood count (CBC),electrolytes, blood urea nitrogen (BUN)/ creatinine, glucose,
and urine analysis, were within normal range except leukocytosis (WBC 26,800/mm3)and increase
creatinine level ( 2.4 mg/dL). The electrocardiogram (ECG) was interrupted as sinus tachycardia
with no other pathological abnormalities. X ray chest was normal. Urethral catheterization produced
a small quantity of urine. Gastric lavage was done in the ED. The patient admitted to the hospital for
further management and treatment, and the management plan was to rehydrate the patient and correct
any electrolyte disturbance. The patient remained hemodynamically stable during the first 8 hours,
then became distressed, shocked and transferred to the intensive care unit (ICU). The family brought
the drug bottle in the second day and it was colchicine 0.6 mg tablet and the patient took nearly 30
mg. We searched for treatment recommendations and As Fab fragments were unavailable for clinical
use, treatment options were limited and only supportive care could be given. Over next 12 hours the
patient clinical condition showed progressive deterioration and became confused, febrile, and more
distressed. Laboratory values revealed a leukocytosis, thrombocytopenia with mild electrolyte
disturbances and elevated liver enzyme levels (a white cell count 24x109/l, platelets 130x109/l, urea
54 mmol/l, creatinine 3.1 mg/dL, INR 3.5. Arterial blood gas results showed a profound metabolic
acidosis (pH 7.2, pCO2 21.8, pO2 68.8, HCO3- 9.9). She received bicarbonate infusions to maintain
PH and showed some improvement (pH 7.3, HCO3- 18)
The patient was started on broad spectrum antibiotic immediately after sent blood and urine culture.
Despite crystalloid solutions and fresh frozen plasma to maintain adequate perfusion pressures. The
patient became hypotensive and unstable and required a dopamine infusion to maintain blood
pressure and few hours later the patient developed respiratory distress and she was required
endotracheal intubation and mechanical ventilation. The patient became less responsive and arrested,
resuscitation started, but she continued to deteriorate and she died on the 3rd day of admission.
Discussion
Colchicine poisoning is an irregular form of drug toxicity and constitute a toxicology emergency of rapid
intervention is required, Colchicine was found to be absorbed rapidly in the ileum of the small intestine after
oral administration. It is digested in the liver by deacetylation to more poisonous oxydicolchicine and
excreted with it is metabolites via the biliary tract by bile explained early symptoms onset of
gastrointestinal. Up to 20% of the quantity used is eliminated the same in the urine [14, 15].
Colchicine toxicity is based on it is antimitotic activity that it binds to cell protein tubulin (Tubuline
works like a receptor for colchicine) and inhibits mitosis in metaphase by blocks spindle formation
by disrupting microtubules [16]. Characteristically colchicine have a short half-life in the blood is
about twenty minutes, due to high affinity to tissues as kidney, liver and spleen where they contain
high concentrations of colchicine, while apparently largely excluded from cardiac and skeletal
muscle as well as brain tissue [16]. Colchicine have direct toxin effect to the abdominal mucous
membrane layers and hematopoietic stem cells, causing severe diarrhea, related to the rapid turnover
of intestinal mucosal cells and decreasing absolute number of short-living blood cells granulocytes
and thrombocytes.
In acute colchicine poisoning, there is a delay of 1-6 hours between ingestion and the development of
toxic symptoms. The clinical presentation may be divided into three stages. The first stage is marked by
the onset of nausea, vomiting, and severe diarrhea with hypovolemia. Stage two 24 hours post ingestion and
may include involvement of any organ system, with bone marrow depression ( pancytopenia) which develop
between 2 and 5 days after ingestion, also respiratory, renal and cardiac failure .[4, 12]. Stage three is seen in
patients who recover from colchicine poisoning and is manifested by transient alopecia and a rebound
leukocytosis. Colchicine toxicity can lead to severe coagulation disturbances[17]. In one case of
colchicine poisonings, the disorder of coagulation disturb were prominent[18]. According to known
toxicological data, colchicine concentration in the brain is low, and can affect the heart causing heart
failure, which consider as an important cause of morbidity in suffers with severe colchicine toxicity
.[19] Echocardiography was performed in all of the patients.[19] Prognosis of colchicine poisoning is
mainly associated with the amount of consumption and the duration after ingestion of the medication
.[20]
The treatment of colchicine poisoning is mainly supportive because there is no antidote prevails.
Although particular treatment such as monoclonal antibodies to colchicine has been revealed in some
case reviews and animal research, but it is not yet from the commercial perspective available, later
on, will possibly enhance the possibility of improve the chance of survival.[21] A forceful
gastrointestinal decontamination with gastric lavage and activated charcoal should be obtained as early
as possible (even in late presentation), it have significant value because of enterohepatic recirculation of the
medication. [22] Neither hemodialysis nor hemoperfusion is particularly effective because of the large
cell distribution of colchicine.[23] For technological reasons, few reviews have been released
calculating the value of colchicine levels in blood or urine. However, a successful result after the use
of colchicine particular Fab fragments has been revealed. Colchicine specific Fab fragments and are
derived from goats and consist of the light chain and variable region of the heavy chain [6]. The
mechanism of action is just like digoxin specific Fab fragments, it have high affinity to colchicine
allows redistribution into the intravascular compartment and this acts for elimination of important
quantities of drug from peripheral sites.[24]
In conclusion, Colchicine overdose associated with a high morbidity and mortality rate due to
multiorgan failure, the severity tends to be related to the dosage of ingested drug and the time of
admission to hospital. Although a specific therapy is not yet available in colchicine poisoning, the
symptomatic treatment should be started as soon as possible. An efforts to create particular strategy
to colchicine intoxication should be strengthened in order to decrease mortality rate in patients taking
drugs in a large amount
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