Successful management of a colchicine overdose with plasmapheresis: a case report

Abstract

An overdose of colchicine can be lethal due to its narrow therapeutic index. We aimed to describe the successful management of a large intentional overdose with plasmapheresis therapy. A 32-year-old female presented to the Emergency Department with nausea, vomiting, and dizziness eight hours after intentionally ingesting 0.9 mg/kg colchicine in tablet form. She was treated with plasmapheresis and supportive therapy. The only abnormality in four days of observation was one-day transient lymphopenia (0.82 x 10⁹/L).

Keywords:

• Colchicine overdose
• deliberate self-harm
• plasmapheresis
• lymphopenia
• case report

Introduction

Colchicine is an antimitotic medicine used in the treatment of acute attacks of familial Mediterranean fever (FMF), gout arthritis, and inflammatory conditions including Behçet disease [1]. Colchicine is a natural alkaloid with anti-inflammatory activity. It is derived from autumn crocus Colchicum autumnale and the glory lily Gloriosa superba [2].

Currently, there is no readily available antidote for colchicine intended for clinical use. Extracorporeal elimination techniques are controversial as colchicine is rapidly distributed to tissues and has a large volume of distribution of about 7 L/kg. We present a case of a large colchicine ingestion that was successfully treated with supportive care and plasmapheresis.

Case report

A 32-year-old female ingested 90 of her husband’s 0.5 mg colchicine tablets (0.9 mg/kg) approximately 8 h prior to presenting to the emergency department. She complained of abdominal pain, nausea, and dizziness. On arrival, she had a heart rate of 130 beats per minute, blood pressure of 90/62 mmHg, respiratory rate of 15 breaths per minute, oxygen saturation of 97% on room air, and temperature of 36.4 degrees Celsius. On physical examination, she was alert and oriented. She had only mild upper abdominal tenderness.

An electrocardiogram (ECG) showed sinus tachycardia. A chest radiograph showed no acute abnormalities. Bedside transthoracic echocardiography showed a left ventricular ejection fraction of 60%. Initial laboratory analysis was remarkable only for a lymphopenia (0.82 x 10⁹/L) (Table 1). Intravenous (IV) hydration and proton pump inhibitor treatments were started. As the patient confirmed ingesting a potentially lethal dose of colchicine, the Medical Toxicology Intensive Care Unit team decided to perform plasmapheresis. For confirmation, blood and urine samples were collected to analyze colchicine concentration before and after plasmapheresis. A one hour plasmapheresis was applied with 10 U fresh frozen plasma (FFP). Her lymphocyte count increased (1.72 x 10⁹/L) immediately after plasmapheresis.

Table 1. Laboratory results during hospitalization.

Hours After Plasmapheresis	WBC (10^9/L)	LYM# (10^9/L)	NEU# (10^9/L)	Urea (mg/dL)	Creatinine (mg/dL)	CK (U/L)
−1	9.05	0.82	7.22	32.2	0.64	81
1	14.4	1.72	11.64	26.2	0.73	193
12	9.93	1.42	8.01	24.3	0.46	308
24	8,33	1.01	6.63	9.6	0.46	362
72	7.55	1.62	4.94	20.4	0.48	277
120	10.44	3.27	5.95	21.7	0.55	96

In our case, the serum colchicine concentration was 1.02 ng/mL before plasmapheresis, 0.91 ng/mL at the first hour and 0.48 ng/mL at the 8th hour after plasmapheresis. The quantitative analysis of serum colchicine concentration was performed on AB-SCIEX Q Trap 5500 LC/MS/MS. The patient was followed closely for 4 days 4 days in the toxicology intensive care unit. During the follow-up, there were no abnormalities in laboratory testing or any additional symptoms. On the fifth day, the patient was transferred to the psychiatry inpatient unit.

Discussion

Early plasmapheresis may prevent significant toxicity from a lethal overdose of colchicine. Colchicine overdose can result in various complications including multiorgan failure, coagulopathy, respiratory failure, neuropathy, renal failure, pancytopenia, and cardiogenic shock. Mortality is high in massive ingestions and there is no available antidote. Colchicine ingestions of >0.5 mg/kg may have high mortality, but lower doses do not assure benign courses [3–5]. There are also case reports that have resulted in mortality even with low colchicine doses so this indicates that there is no clear distinction between non-toxic, toxic or lethal colchicine doses [6,7].

Colchicine is rapidly absorbed in the gastrointestinal tract and is highly lipid soluble with a high volume of distribution (2.2–12 L/kg), and a plasma protein binding capacity that approaches 50%. Colchicine binds to the active site of the tubulin, thereby disrupting the microtubular communication in the cell [6]. Although colchicine is taken up equally in all cells, it disrupts the mitotic spindle apparatus in rapidly dividing cells including cells in the gastrointestinal tract and bone marrow, and skin cells [1]. Colchicine overdose may cause thrombocytopenia, leukopenia, neutropenia, anemia, inhibition of interleukin-2 receptor expression on activated T lymphocytes, and dose-dependent inhibition of human mixed lymphocyte response resulting in reduced lymphocyte function [8–11].

The management of colchicine overdose is primarily supportive. Additionally, multi-dose activated charcoal may be beneficial, even beyond the first hour post-ingestion because colchicine undergoes enterohepatic recirculation [6,12]. Plasmapheresis is a medical procedure that utilizes extracorporeal plasma separation techniques, such as centrifugation or membrane filtration, to separate plasma from blood. The extracted plasma is then replaced with a replacement fluid, while the remaining blood components are returned to the patient’s body. It is used to treat autoimmune disorders, neurological disorders, and some poisonings or drug overdoses [13]. Plasmapheresis filters the blood and eliminates harmful antibodies, similar to dialysis. However, plasmapheresis is specifically designed to remove antibodies from the plasma component of the blood. During plasmapheresis, the plasma that has been filtered out is removed, and red blood cells are returned to the patient along with a replacement fluid. It is not a commonly used extracorporeal elimination method in clinical toxicology, but may be considered in cases where a toxin has high plasma protein binding and a low volume of distribution [14]. There are limited case-level studies showing that the benefits of extracorporeal methods for colchicine overdose in the literature [15]. Indeed, the use of extracorporeal therapies for the purpose of colchicine removal would theoretically be limited by a large volume of distribution. Schaffer et al. successfully treated a colchicine poisoning case with persistent metabolic acidosis with continuous renal replacement therapy (CRRT) [15]. Wacker et al. successfully treated a patient with poisoning due to unintentional colchicine intake with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and total plasma exchange [16]. Mullins et al. showed that impaired renal function can occur in colchicine overdose [17]. Beyond elimination of colchicine, extracorporeal methods may have a therapeutic role in colchicine poisoning to manage severe metabolic acidemia and renal failure. Ramezani et al. successfully treated a patient with colchicine overdose with hemodialysis and hemoperfusion [18].

Colchicine’s effective steady state serum concentrations with therapeutic use range from 0.5 to 3 ng/mL, with toxic effects occurring at a concentration of approximately 3 ng/mL or higher. However, serum concentration may be a poor indicator of efficacy and toxicity given binding to albumin and a large steady state volume of distribution [19]. In our case, serum colchicine concentrations were measured before and after plasmapheresis. Given the elimination half-life of colchicine ranges from 20-40 h, a decrease in colchicine concentration immediately after plasmapheresis suggests that this modality may be effective at rapidly reducing serum colchicine concentrations [20].

Conclusion

Early plasmapheresis may prevent significant toxicity from a lethal overdose of colchicine. In addition to close hemodynamic monitoring, critical and supportive care are the mainstays of treatment. We successfully treated a case of high-dose colchicine intake with lymphopenia using plasmapheresis.

Acknowledgements

We extend our gratitude to Dr. Ramazan Güven of the Basaksehir Cam and Sakura City Hospital, Department of Emergency Medicine at University of Health Sciences, for his valuable input in drafting the manuscript. Additionally, we acknowledge Dr. Hüseyin Çetin Ketenci from the Department of Forensic Sciences at Recep Tayyip Erdoğan University Faculty of Medicine for his assistance in measuring serum colchicine concentrations.

Disclosure statement of interest

The authors have no financial or other interest in the medicine or treatment described in the article.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.