Colchicine toxicity in a suicidal attempt: attention to patients’ relatives’ psychological health

Manuscript type : Case Report | Article Date : 2015/04/18

  • Autors

    1. Sharifi Amirsina
    2. Ziaee Vahid
    3. Mahmoudi Ghafar-Ali
  • Abstract

    Colchicine is an old well-known drug commonly used in treatment of gout and familial mediterranean fever. Fatal colchicine intoxication has been reported in accidental or intentional accidents. Multiorgan failure or subsequent sepsis due to myelosuppression, are the main cause of death in these cases. The wide lethal dose of 7-90 mg has been reported in previous studies. We reported colchicine intoxication in 18 year-old-female who ingested 30 mg of her brother who was treated for FMF. Heart failure, renal failure and hepatic failure resulting in disseminated intravenous coagulopathy caused unresponsive cardiopulmonary arrest after 65 hours post ingestion. Precise control of number of tablets prescribed for patients especially drugs with narrow therapeutic index like colchicine should be considered. Great burden of chronic disease in families should draw attention to psychological health of patients’ family.
  • Description

    INTRODUCTION

    Colchicine is a liposoluble alkaloid extracted from Colchicum autumnale and related species.1 Anti-in-flammatory effect through prevention of activation, degranulation, and migration of neutrophils made col-chicines an appropriate medication for treatment and control of gout, familial Mediterranean fever, biliary cirrhosis, amyloidosis, and condyloma acuminate.2-3 Despite advantageous effects on disease control, it has very narrow therapeutic index which makes it a drug of great hazardous potency for accidental over-dose or suicidal attempt. So far, it was impossible to definitely describe lethal dose of colchicine. As there was case of fatal poisoning by ingestion of 7 mg while the other patient survived ingestion of 90 mg but it is known that ingestion of over 0.8 mg/kg would be definitely fatal.4-5Colchicine toxicity is well described in 3 stages.6-8 It has been reported that tablets, powder and even the plant itself can cause the same clinical manifestation of colchicine toxicity which is associat-ed with high mortality rate.9.The first stage is marked by peripheral leukocytosis, gastrointestinal symp-toms like nausea, vomiting, abdominal pain, diarrhea and massive fluid and electrolytes losses which lead to consequent hypo-volemic shock after 4 - 12 hours. During 24 - 72 hours the second stage of intoxica-tion would happen. It is characterized by multiorgan failure and would last for 5- 7 days. Heart failure, arrhythmias, renal failure, hepatic injury, respirato-ry distress, coagulopathies, bone marrow depression and neuro-muscular involvement are known to be the most common manifestations of this stage. The third stage, described as leukocytosis and alopecia, is only seen in patients who survived the multiorgan failure.6-8 Colchicine will be metabolized by the P-gp and CY-P3A4 in the liver in a first-order process. Biliary ex-cretion and enterohepatic recirculation will result in elimination of the drug through feces.10 20% of un-changed colchicine elimination will be through renal excretion, which may be increased if previous liver failure existed.11 We present the first known case of colchicine toxicity in one of the relatives of patient with FMF in suicidal attempt in Iran.

    CASE REPORT

    A-18-year-old female was admitted to a hospital in rural distinct of Lorestan, Iran for attempting suicide. She had ingested 30mg (60 tablets of 0.5 mg) of her brother’s colchicine 3 hours prior to admission. Her past medical history was unremarkable and she was never on specific medication for long term. There was no other drug co-ingested as her parents find emp-ty pack of her brother’s colchicine in her hands. Her brother had a history of FMF. At presentation she was conscious and orientated. She complained nausea and mild abdominal pain with normal vital signs (blood pressure: 112/83 mmHg; axillary body temperature: 36.5°C; respiratory rate: 15 breaths/minute; and heart rate: 72 bmp). She had unremarkable examination. Stomach lavage was performed, and she was trans-ferred to the tertiary hospital 11 hours after ingestion. At our center, she developed diarrhea and her nausea and vomiting got worsened. She also developed met-abolic acidosis (pH: 7.28; partial pressure of carbon dioxide (pCO2): 39 mmHg; (bicarbonate) HCO3: 16 mmol/L. Sodium bicarbonate and intravenous fluids were administered to treat acidosis. Hematological studies revealed serum hemoglobin level of 14.5g/dl; serum leukocyte count: 9100/mm3; serum platelet count: 266000/mm3; prothrombin time of 27.7 sec-onds; international normalized ratio (INR) of 2.21 and activated partial thromboplastin time (aPTT) of 28.8 seconds. Serum biochemistry results were as follows: BUN: 33 mg/dl; creatinine: 1.3 mg/dl; glucose: 70 mg/dl; Na: 139.8 mEq/L; K: 3.7 mEq/L. Gastric lavage was performed again and activated charcoal was given every 6 hours at the dose of 0.25 g/Kg/h. Despite re-suscitation she developed multiorgan failure 40 hours after cholchicine ingestion. She had evidence of heart failure (continuous low central venous pressure and elevated myocardial enzyme was detected), renal failure (insufficient urine output and elevated BUN and creatinine levels), hepatic failure (elevated levels of serum aminotransferases and total bilirubin). Intra-venous fluids and positive inotropic agents were used and hemodialysis was performed. On the follow up, blood tests showed raised D-dimer, aPTT, PT time and INR, and decreased fibrinogen. Based on these findings disseminated intravascular coagulopathy (DIC) was diagnosed and the fresh frozen plasma and pack cell infusion was ordered. At 50 hours after ingestion, her general condition got worse (heart rate of 124 bpm, respiratory rate of 35 breaths/minute, peripheral oxygen saturation of 94%, Glasgow coma scale of 11, and central venous pres-sure of 80/53 mmHg). At 62 hours after ingestion, she developed cardio-pulmonary arrest and responded to resuscitation after 40minutes. Hemodialysis and supportive treatments were continued. At 65 hours after ingestion, she de-veloped cardiopulmonary arrest which remained completely unresponsive and she died because of persistent metabolic acidosis, DIC, and multiorgan failure.

    DISCUSSION

    Colchicine intoxication disrupts cytoskeletal function through inhibition of β tubulin polymerization into microtubules affecting the organs with high mitot-ic activity the most. Thus, mitosis and intracellular transport system are disabled.2-3 Bismuth et al defined the clinical manifestations and prognosis of different doses toxication. It is believed that minor toxicity after ingestion of less than 0.5 mg/kg of colchicine will be preceded by 100% survival, while major toxicity after ingestion of 0.5–0.8 mg/kg will cause 10% mortality and mortality would be ab-solute consequence of ingesting 0.8 mg/kg or more.12 The time interval between colchicine intake and the initiation of therapeutic interventions is another fac-tor influencing survival. Absorption of colchicine in gastrointestinal tracts is highly variable. It has been estimated to take 30 - 120 minutes to absorb after oral ingestion. Thus, the treatment course and survival rate would be affected if initiation of treatment post-pone more than 2 hours after ingestion of colchicine.11 However, cases of colchicine intoxication despite of immediate presentation and early onset of treatment is reported.7 Different aspects of colchicine toxicity have been proposed to be the main lethal factor. As Mullins et al, described arrhythmia and cardiac insufficiency [13],and Sauder et al described myocarditis.14 Erden et al proposed that early leukocytosis may be a pre-dictor for mortality [8]. In this regard, van Heyningen et al suggested that monitoring of serum troponin I levels every 6–12 hours would predict cardiovascu-lar collapse and would be a guide for more intensive management.15 It’s believed that DIC formation is a result of exces-sive fibrinolytic activity and multiorgan failure.8 Treatment of colchicine intoxication is based on supportive therapy.16 The most important point is to compensate the fluid losses. Thus, central venous pressure monitoring for hemodynamic status and uri-nary output charting are necessary. Gastric lavage and activated charcoal are used to prevent absorption via gastrointestinal track.17-18 Baud et al reported a successful treatment of a wom-an who ingested 60 mg of colchicine in suicidal at-tempt by administration of colchicine-specific Fab fragments antibodies.19 Although this treatment is not commercially available but is should be considered as a new treatment choice. In this case we reported a suicidal attempt in a-18-year-old-female, who was sister of a patient with FMF. Her medical record was unremarkable for pre-vious major depression disorder but having a family member in a poor condition suffering from chronic illness would affect every individuals. So psycholog-ical support of patients’ families is as important as patients themselves.

    CONCLUSION

    Colchicine intoxication is associated with high mor-tality rate due to multiorgan failure. It is important to inform patients about its potential lethality and give them an understandable explanation of side effects. A careful watch must be arranged for patients, which can be obtained by close visiting intervals and prescribing limited number of tablets until the next visit, in order to avoid accidental or intentional overdose.
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