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. The drug recently became more widely used for the treatment of many rheumatological and nonrheumatological conditions including pseudogout, familial Mediterranean fever amyloidosis , scleroderma, sarcoidosis, Bechet's disease  Paget's disease,  psoriasis. primary biliary cirrhosis  and alcoholic cirrhosis . Although colchicine poisoning is an uncommon form of drug overdose, but can lead to severe multi organ failure in overdose. 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, while patients have survived after ingestions of more than 60 mg.  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. Several authors reported the occurrence of myoneuropathy and myopathy , especially in association with renal impairment . rhabdomyolysis also reported.. 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 . 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 . 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. In one case of colchicine poisonings, the disorder of coagulation disturb were prominent. 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 . Echocardiography was performed in all of the patients. Prognosis of colchicine poisoning is mainly associated with the amount of consumption and the duration after ingestion of the medication . 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. 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.  Neither hemodialysis nor hemoperfusion is particularly effective because of the large cell distribution of colchicine. 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 . 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. 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 References 1. 2. 3. 4. 5. 6. A.P. Insel. Drugs employed in the treatment of gout. In (1999). 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