Combination of Multiple-Dose Activated Charcoal and Infusion Therapy That Led to Favorable Outcomes in Colchicine Poisoning: A Case Report

Introduction

Colchicine is a lipophilic alkaloid used to treat gout flares. Its therapeutic margin is narrow, and peak plasma concentrations (Cmax) are reported to be 6.50 ± 1.03 ng/mL at 1.07 ± 0.55 hours (Tmax) after oral administration [1]. Toxicity occurs easily without the ingestion of markedly high doses. Colchicum autumnale, a lily plant, is widely available as an ornamental plant and has been associated with colchicine poisoning, which can lead to multiple organ failure and other serious complications [2,3]. After oral administration, colchicine is readily absorbed and undergoes extensive first-pass metabolism. It is primarily metabolized by the liver, undergoes significant enterohepatic recirculation, and is excreted by the kidneys [4]. Ferron et al detected a secondary peak within 6 hours of oral administration, indicating enterohepatic recirculation [1]. Colchicine-specific Fab fragments can be effective in treating colchicine poisoning; however, they are not readily available. No standard treatment is available, and patients are treated symptomatically [5,6]. Because colchicine undergoes enterohepatic recirculation, multiple-dose activated charcoal (MDAC) reportedly eliminates it. Renal excretion may also be important in patients with extremely high serum colchicine levels. However, few reports have simultaneously monitored serial serum and urine colchicine concentrations alongside a detailed treatment timeline, limiting understanding of the relative contributions of these pathways.

Case Report

A man in his 20s was transferred to the emergency department (ED) with nausea, vomiting, diarrhea, drowsiness, and dyspnea. He had previously been treated for autism spectrum disorder and attention-deficit hyperactivity disorder but was taking no home medications at the time of admission. This was the patient’s first episode of intentional overdose; no prior history of self-poisoning was documented. On arrival at the ED, he reported ingesting 2 dried Colchicum autumnale bulbs, with an estimated colchicine content of 6.24 to 15.6 mg, based on published colchicine concentrations of 0.08% to 0.2% by dry weight [7]. The actual bulb weight was not measured, and plant identification relied on the patient’s verbal report alone. The bulbs were ingested with an energy drink of an unknown type and volume at 27 hours prior to admission (27 hours post ingestion [h-PI]). The patient’s body weight was 56 kg (estimated intake: 0.111–0.279 mg/kg). Doses above 0.5 mg/kg have been associated with severe toxicity, and doses of approximately 0.8 mg/kg or greater have been reported to carry a high risk of fatal outcome, although considerable inter-individual variability exists [4,8]. He was conscious (Glasgow Coma Scale: E4V5M6) and hemodynamically stable, with a blood pressure of 150/79 mm Hg, heart rate of 90 beats/min, respiratory rate of 20 breaths/min, body temperature of 36.7 °C, and SpO2 of 99% in room air. Physical examination revealed facial flushing and ocular conjunctival hyperemia. Chest radiography, electrocardiography, and echocardiography revealed no abnormalities. Blood alcohol screening was performed on admission (result: below detectable limit); no multi-drug toxicology screen was performed. No significant irregularities were observed in the initial laboratory values (Table 1). Serial laboratory data including complete blood count, coagulation, hepatic function, lactate, renal function, and electrolytes across 7 time points are shown in Table 1. All values remained within normal limits throughout hospitalization or showed only minor transient fluctuations without clinical significance. Activated charcoal (1 g/kg) and sodium picosulphate hydrate (75 mg) were administered via nasogastric tube. The patient was admitted to the intensive care unit (ICU). MDAC (activated charcoal 0.5 g/kg every 6 h, 13 doses total) and blood purification therapy, consisting of 1 session of hemodialysis (HD; cellulose triacetate 0.9 m2, blood flow rate [QB] 100 mL/min, dialysate flow rate [QD] 500 mL/min, 4.2 h) and 2 sessions of hemodiafiltration (HDF; polysulfone 1.5 m2, QB 100 mL/min, QD 500 mL/min, 3.75 h), were administered for toxin removal. The 13-dose MDAC regimen was planned from admission based on clinical severity and the expected duration of enterohepatic recirculation. Serum colchicine concentrations were measured retrospectively by liquid chromatography–tandem mass spectrometry (LC-MS/MS) and were not available to the treating team during hospitalization. Serum and urine colchicine levels were measured using a commercially available drug and toxicant rapid screening system based on LC-MS/MS (Shimadzu Corporation, Kyoto, Japan) at the Division of Toxicology, Department of Pharmacobiology, Showa University Graduate School of Pharmacy. A case-specific analytical validation was not performed; the assay was not independently validated for the purposes of this report. Fluid resuscitation with Ringer’s acetate was initiated at approximately 270 mL/h and subsequently titrated (60–200 mL/h) based on clinical assessment and fluid balance (Table 2). The complete intervention and monitoring timeline is presented in Table 3. Activated charcoal passage in stool was confirmed visually at approximately 32, 43, 55, and 70 h-PI. Safety during MDAC administration was monitored daily by clinical assessment, serial blood tests (complete blood count, renal function, electrolytes, and hepatic function), and chest and abdominal radiography. No adverse events related to MDAC, including bowel obstruction or electrolyte disturbances, were observed. Two days after ingestion, electrocardiography revealed slight QT prolongation (QTc, 451 ms) and sporadic premature ventricular contractions; however, no other specific symptoms were noted.

The serum colchicine level (Figure 1) was 50.3 ng/mL at 27 h-PI (on arrival). It decreased to 21.2 ng/mL at 35 h-PI, temporally associated with initiation of fluid infusion and activated charcoal, and further to 12.16 ng/mL immediately before HD (48.0 h-PI; circuit line). After HD, the level was 5.46 ng/mL (52.2 h-PI; circuit line). Before HDF1, the level was 3.98 ng/mL (65.0 h-PI; peripheral vein). The next available sample, which was obtained approximately 2.4 hours after HDF1 completion, was 17.74 ng/mL (77.0 h-PI), representing a secondary rise. Before HDF2, the level was 2.54 ng/mL (89.0 h-PI); the subsequent sample at 113.0 h-PI was 5.24 ng/mL. No samples were drawn immediately before or after the HDF sessions via the extracorporeal circuit, limiting interpretation of HDF-specific effects. The urine colchicine level was 110.0 ng/mL at 29 h-PI (timed specimen), then gradually decreased through 89 h-PI. A spot urine at 117 h-PI confirmed further decline. Urine creatinine levels fell markedly between 41 and 53 h-PI (429.7 to 43.5 mg/dL), likely reflecting dilution from high-volume infusion. Urinary excretion rates could not be calculated without concurrent urine volumes. Renal function remained preserved throughout (creatinine 0.53–0.65 mg/dL; estimated glomerular filtration rate [eGFR] > 130 mL/min/1.73 m2).

The patient was discharged on the fifth day of hospitalization after a psychiatric consultation, and was followed up as an outpatient. No obvious abnormalities were observed after hospitalization.

The CARE guidelines were followed in the preparation of this case report.

Discussion

LIMITATIONS:

This case has several important limitations. First, multiple interventions (MDAC, high-volume fluid therapy, HD, and HDF) were administered concurrently, precluding attribution of observed concentration changes to any single therapy. Second, renal clearance cannot be quantified from the available data, as urine volume was not measured at individual colchicine sampling intervals, and urine creatinine was available at only 2 time points. Urine colchicine concentrations were neither corrected for urine volume nor normalized by urine creatinine; therefore, these data reflect concentration only and should not be interpreted as reflecting excretion rate or renal clearance. Third, no serum samples were drawn immediately before HDF1/HDF2 start or immediately after HDF end from the circuit line; post-HDF values likely reflect a mixed signal of HDF effects and post-session redistribution. Fourth, plant identification relied solely on the patient’s verbal report, and the dose estimate was based on published colchicine content ranges without weighing the actual material. Fifth, no comprehensive multi-drug toxicology screen was performed (only alcohol screening, which was below the detection limit), and the energy drink’s composition and quantity were unknown; these factors cannot be excluded as potential contributors to the observed kinetics. Sixth, colchicine concentrations were measured using a commercially available LC-MS/MS screening platform (Shimadzu Corp); a case-specific analytical validation was not performed, and the assay was not independently validated for the purposes of this report. These limitations should be considered when interpreting the findings, which are presented as hypothesis-generating observations rather than definitive conclusions.

Conclusions

The most common symptoms of colchicine poisoning are gastrointestinal, including nausea, vomiting, diarrhea, and dehydration. In this case, serial monitoring of serum and urine colchicine over a detailed treatment timeline revealed temporal associations between fluid therapy, MDAC administration, and concentration changes. These findings support the hypothesis that promotion of renal excretion through fluid therapy and inhibition of colchicine reabsorption from the enterohepatic circulation using MDAC may contribute to colchicine elimination, while acknowledging that concurrent interventions and the absence of quantitative clearance data preclude definitive conclusions.