Acute Pediatric Colchicine Toxicity is Associated with Marked Bradydysrhythmias.

BACKGROUND: Colchicine ingestion is rare but highly lethal. Patients usually die of multiorgan failure and cardiogenic shock. Colchicine is not only associated with depressed myocardial function but also with fatal heart rhythm disturbances, such as complete heart block, ventricular tachycardia, and asystole. While histologic changes of myocytes are well known, the mechanism by which colchicine affects cardiac impulse generation and conduction is not fully understood. CASE REPORT: We present a case of colchicine ingestion with sinus bradycardia, marked sinus arrhythmia, and first- and second-degree heart block. A 10-year-old previously healthy boy was brought to the emergency department for the sudden onset of dizziness, abdominal pain, and vomiting after ingesting his grandfather's colchicine and furosemide. His symptoms improved with ondansetron and intravenous normal saline. However, because of the colchicine ingestion, he was admitted to the pediatric intensive care unit for observation. He first developed PR prolongation (∼4-30 h postingestion) followed by marked sinus bradycardia and sinus arrhythmia along with second-degree heart block (∼48-60 hours postingestion). The minimum heart rate was 40 beats/min. Marked sinus arrhythmia was observed, suggesting an increase in parasympathetic activity. His heart rhythm improved initially with less sinus arrhythmia followed by resolution of heart block. He was discharged home without any sequelae. Holter monitoring 1 week after discharge showed normal heart rate variability for age. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case provides novel insights into how colchicine may affect the heart's electrophysiology. Colchicine may increase the parasympathetic tone enough to cause sinus bradycardia and different degrees of heart block.

An Insidious Danger in Children With Familial Mediterranean Fever: Colchicine Intoxication.

Colchicine is an anti-inflammatory drug, which has been used for the treatment of familial Mediterranean fever for several decades with narrow therapeutic-toxicity window. Colchicine poisoning is rare but frequently a life-threatening emergency condition in pediatric practice. It may occur by excessive ingestion of colchicine tablets accidentally or intentionally. Herein, we report a suicide attempt with colchicine in a 12-year-old girl who had been followed up with the diagnosis of familial Mediterranean fever. She was admitted to our emergency department with gastrointestinal complaints and subsequently died because of the rapidly deteriorating metabolic and hemodynamic conditions.

Toxic encephalopathy due to colchicine--Gloriosa superba poisoning.

Gloriosa superba, a flowering plant widespread in South and Southeast Asia, is implicated in many cases of self-poisoning. Colchicine is concentrated in the seeds and tubers and this mediates its toxicity. We describe a 28-year-old woman who developed delayed encephalopathy after eating G superba tubers. MR scan of brain showed bilateral symmetrical T2 basal ganglia hyperintensities in the caudate and lentiform nuclei. The delay in onset of encephalopathy is attributable to a direct-effect colchicine, probably mediated through its effect on microtubular transport.

Long-term outcome after suicidal colchicine intoxication in a 14-year-old girl: case report and review of literature.

BACKGROUND: Colchicine is used as an anti-inflammatory drug in the treatment of gout, familial Mediterranean fever, and Behçet disease. However, because of its potent inhibition of mitosis, adverse effects and symptoms of intoxication are frequent. Clinical manifestations of colchicine intoxication include abdominal cramps, diarrhea, and multiorgan failure including cardiovascular collapse with fatal outcome. OBJECTIVE: We report here the case of a 14-year-old girl who ingested 12.5 mg (0.23 mg/kg body weight) colchicine in a suicide attempt. CASE REPORT: Major complaints of this fully conscious patient at the time of presentation ∼2 hours after ingestion of colchicine were nausea and impaired vision. Apart from a colchicine serum concentration of 16.2 ng/mL, no abnormalities were seen in the physical examination and blood tests. Gastrointestinal decontamination by activated charcoal, repeated administrations of sodium sulfate (Glauber salt) and substitution of volume and electrolytes led to complete recovery.

[Colchicine poisoning: a case report]. / A propos d'une intoxication létale à la colchicine.

Colchicine is a drug commonly used for treatment of acute and chronic gout. Poisoning is a rare but always serious event. The purpose of this report is to describe the case of a 16-year-old girl who ingested an unknown amount of colchicine in a suicide attempt. At the time of admission she presented with gastrointestinal manifestations and reduced consciousness. After ten days in the intensive care unit she died due to multiple organ failure. This case provides the opportunity not only to review the clinical course and prognostic factors associated with colchicine poisoning but also to underline the difficulty of its management due to the absence of a specific antidote and of emergency pharmacologic doses.

[Colchicine intoxication in four elderly patients: how to prevent it?]. / Risque d'intoxication à la colchicine chez les personnes âgées et moyens de prévention: à propos de quatre observations.

INTRODUCTION: In France, unlike other countries, the use of colchicine is preferred to other anti-inflammatory drugs for the treatment of gout. CASE REPORTS: We report a case series of four elderly patients (range from 72 to 83 years of age) who presented with colchicine intoxication, all notified to the Basse-Normandie pharmacovigilance centre in 2007. For each patient, one or more risk factors were identified: renal failure, high initial dosage, absence of laboratory monitoring. CONCLUSION: It would be useful to establish specific guidelines for colchicine use in the elderly population.

Colchicine intoxication and infection risk: a case report.

Colchicine is widely used, primarily for the treatment of gouty arthritis and familial Mediterranean fever. Colchicine intoxication is a rare but potentially life-threatening event. Herein, we reported a 26-year-old woman who presented to the emergency department after ingesting 27.5 mg of colchicine in a suicide attempt. She exhibited signs typical of colchicine-poisoning and developed infectious complications but with subsequent complete recovery. This paper discusses the role of colchicine poisoning in increasing susceptibility to infections. This aspect is usually under-appreciated in the clinical picture of colchicine overdose.

Liquid chromatography-tandem mass spectrometry for the determination of colchicine in postmortem body fluids. Case report of two fatalities and review of the literature.

Poisoning by colchicine may occur following ingestion of this alkaloid used for the treatment of acute gouty arthritis. The authors report two fatalities and describe a liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS-MS) triple-quadrupole method for the determination of colchicine in autopsy samples. One milliliter of heart blood, femoral blood, urine, bile, gastric, and vitreous each were extracted with saturated NH4Cl at pH 9.6 and dichloromethane/5% isopropanol. Separation was achieved on a C18-Xterra column with a mobile phase consisting of 2 mM ammonium formate buffer (pH 3)/acetonitrile in a gradient mode. Four product ions of the protonated molecule were monitored. The method was fully validated in whole blood (1 mL) and was linear in the range of 0.5-50 ng/mL (r2>0.99). The limit of detection was 0.1 ng/mL (50 times S/N), and the limit of quantitation was 0.5 ng/mL with RSDs<11.8% intraday (n=6), <18.7% interday (n=18), and accuracy<3% (n=18). Case #1: a 33-year-old nurse committed suicide by the ingestion of 80 colchicine 1-mg tablets. She died 61 h later after resuscitation procedures. Colchicine was found in heart blood at 5.2 ng/mL, femoral blood at 17.4 ng/mL, urine at 19.4 ng/mL, bile at 42.8 ng/mL, gastric at 348 ng/mL, and vitreous at 3 ng/mL. Case #2: a 57-year-old man with gout was found dead at home. Colchicine was found in heart blood at 22.8 ng/mL, femoral blood at 21.9 ng/mL, lung blood at 45.2 ng/mL, urine at 148.5 ng/mL, bile at 1818.5 ng/mL, gastric at 219.8 ng/mL, and vitreous at 0.5 ng/mL. These results were consistent with death. Because of its good sensitivity, this LC-ESI-MS-MS triple-quadrupole method is suitable for the determination of colchicine not only in fatalities but also for pharmacokinetic studies.

Troponin for prediction of cardiovascular collapse in acute colchicine overdose.

The use of colchicine, a treatment for acute gout and familial Mediterranean fever, is limited by its toxicity. A relatively low dose of colchicine may be fatal. After a colchicine overdose, monitoring should include 6-12 hourly serum troponin measurements. A rising troponin level predicts cardiovascular collapse and is an indication for more intensive management.

Epithelial cell mitotic arrest--a useful postmortem histologic marker in cases of possible colchicine toxicity.

Following ingestion of 30 mg of presumed benztropine (Cogentin) a 39-year-old male developed nausea, vomiting and diarrhea. His admission to hospital was soon followed by collapse and death. Histological examination, however, revealed increased numbers of mitotic figures in otherwise normal epithelial cells of the esophagus and bronchioles, a feature characteristic of colchicine toxicity. Subsequent toxicological analyses confirmed the presence of colchicine in the urine, but not in the blood. A dispensing error had resulted in substitution of colchicine for Cogentin. Histological findings had, therefore, provided evidence of colchicine toxicity and had guided subsequent toxicological evaluation. In suspected cases of colchicine toxicity, histological samples should, therefore, be taken from multiple sites along the gastrointestinal and respiratory tract in addition to other organs and tissues so that diagnostic morphological changes can be looked for.

Colchicine poisoning: case report of two suicides.

Colchicine overdose is uncommon but potentially life threatening because of the high toxicity of the drug. Poisoning by colchicine may occur following ingestion of medication used in acute attacks of gout and inflammatory diseases. We describe two cases involving suicide by the ingestion of medications marketed in France. In case 1, only heart blood was taken after body external examination. In case 2 an autopsy was performed and heart blood, urine, gastric contents and bile were taken for toxicological analysis. Colchicine was assayed in biological specimens by an HPLC-DAD method, after extraction by dichloromethane at pH 8, adding prazepam as internal standard (IS). Analyses were performed on a Symetry C-8 column. Mobile phase was a gradient of acetonitrile/pH 3.8 phosphate buffer. Colchicine is eluted at 13.1 min and the method is linear for blood, urine and bile over the range 4-1000 ng/mL. LOQ is 4 ng/mL. The concentrations of colchicine detected are: case 1: heart blood 13 ng/mL; case 2: heart blood 66 ng/mL, urine 500 ng/mL, gastric content 12 ng/mL, bile 5632 ng/mL. Our findings are in the range of lethal concentrations previously described, but there is no correlation with the amount of ingested drug. Even after massive overdose, it could be impossible to detect colchicine in blood, and as there is a widespread enterohepatic recirculation before excretion in bile and feces, bile is the target sample to analyse. We conclude in both cases that the cause of death was suicide with colchicine. It appears very important to perform an autopsy in order to obtain bile, urine, heart blood and femoral blood.

Colchicine poisoning: report of a fatal case and presentation of an HPLC procedure for body fluid and tissue analyses.

A case involving a suicidal overdose resulting from the ingestion of colchicine tablets is presented. The drug was quantitated using liquid chromatography. The femoral blood level was 62 ng/mL, and the maximum concentration found in bile was 2921 ng/mL. Therefore, bile appears to be the sample of choice for toxicological analysis when a poisoning case involving colchicine is suspected.

Application of LC-MS analysis to a colchicine fatality.

A 73-year-old man developed nausea, vomiting, and diarrhea 20-30 min after receiving a 1.0 mg intravenous dose of colchicine for the treatment of severe pain due to gouty arthritis in his physician's office. He was hospitalized 8 h later, and his condition deteriorated as he developed renal and respiratory failure. He subsequently died 10 h later, or a total of 18 h after he received the original 1 mg colchicine injection. The patient received a prescription for oral 0.6 mg colchicine tablets 8 days previously and consumed eight tablets during that period, an average of 0.6 mg/day (42 of 50 tablets remained at the time of death). Colchicine concentrations were measured by liquid chromatography-mass spectrometry in selected ion monitoring mode using positive ionization. Chromatography was performed using an Eclipse XDB C8 analytical column (30 mm x 2.1-mm i.d., 3-microm particle size) and a programmed mobile phase consisting of 50 mM pH 4 ammonium acetate buffer and acetonitrile. Colchicine concentrations were as follows: 50 microg/L in cardiac blood, 10 microg/L in vitreous humor, 575 microg/kg in liver, 12,000 microg/L in bile, and 4.4 microg in 60 g received gastric contents (estimated total gastric contents 100 g). The cause of death was ruled to be "acute colchicine toxicity" and the manner of death "accidental."

Markedly altered colchicine kinetics in a fatal intoxication: examination of contributing factors.

1. Colchicine poisoning, which is relatively rare, is associated with significant morbidity and mortality. Whilst a new treatment modality, in the form of colchicine-specific Fab fragments is on the horizon, currently available therapy is largely supportive. 2. The elimination of colchicine occurs primarily by hepatic metabolism, following a first-order process, with significant enterohepatic circulation. Renal extraction is responsible for approximately 20% of colchicine elimination. 3. We report a case of colchicine intoxication, complicated by the presence of co-ingestants, in which serum colchicine concentrations remained quasi-constant over the 3 days of the patient's survival, consistent with marked alterations both in metabolism and excretion. The initial presentation was relatively benign but the subsequent course was one of severe colchicine poisoning, resulting in death. 4. Severe colchicine toxicity appears to have resulted in a vicious cycle of progressive organ dysfunction and impaired elimination. 5. Josamycin, one of the co-ingestants and an inhibitor of P-glycoprotein, the membrane pump responsible for multidrug resistance, may have played a significant role in impeding the cellular and biliary elimination of colchicine. Co-ingested opioid and anticholinergic compounds may have altered colchicine absorption and gastrointestinal transit. 6. This case serves as a reminder of the need for attention to co-ingested drugs, to early aggressive therapy, and if available, to consideration of immunotherapy.