a) PHASE I (0 TO 24 HOURS) – GASTROINTESTINAL: Nausea, vomiting, diarrhea (bloody), abdominal pain, dehydration, leukocytosis, volume depletion, and hypotension.
b) PHASE II (1 TO 7 DAYS) – MULTIORGAN SYSTEM FAILURE: Possible risk of sudden cardiac death, dysrhythmias; confusion, coma, seizures; pancytopenia, renal failure, hepatic failure, sepsis, acute lung injury, electrolyte imbalances, rhabdomyolysis. Patients with severe overdose may die during this phase.
c) PHASE III (OVER 7 DAYS) – RECOVERY OR DEATH: Alopecia; myopathy, neuropathy, myoneuropathy, or rebound leukocytosis; death usually is caused by respiratory failure, intractable shock, dysrhythmias, and cardiovascular collapse.

a) CASE REPORT: A case of systemic poisoning was accompanied by keratitis, hypopyon, cataract, pupillary membrane, and disturbance of eye movements (Grant & Schuman, 1993).

a) In one case, serum troponin I (TnI) was elevated in a 17-year-old with myocardial depression secondary to severe colchicine poisoning. Early monitoring for TnI and echocardiography may alert to an impending cardiovascular collapse (Mullins et al, 2000).
b) CASE REPORT: Myocardial injury with elevated ST segment, decreased cardiac contractility, and decreased pulmonary artery wedge pressure was reported in a 15-year-old patient who ingested 24 mg (Murray et al, 1983).
c) CASE REPORT: Colchicine cardiotoxicity has been reported following ingestion of Gloriosa superba tubers. The patient developed severe chest pain, dyspnea, clinical features of acute left ventricular failure, and ST-T wave abnormalities (Mendis, 1989).
d) Decreased cardiac index and increased systemic vascular resistance have been reported (Sauder et al, 1983; Baud et al, 1995).

a) CASE REPORT - Complete atrioventricular block and death were reported in a 60-year-old patient who received IV colchicine for 2 days for acute gout (Wallace & Singer, 1988).

a) CASE REPORT: Sudden cardiac asystole and death were reported in 2 severely poisoned patients. Cardiac arrest occurred at 38 and 51 hours postingestion (Stapczynski et al, 1981).
b) CASE REPORT: Several episodes of bradycardia followed by asystole were reported in a 15-year-old who ingested 18 mg. Death occurred following the fourth cardiac arrest (Hobson & Rankin, 1986).
c) CASE REPORT: A 59-year-old man developed a sudden change in cardiac rhythm approximately 24 hours after a multiple drug ingestion (colchicine, acetaminophen with codeine, trazodone, loperamide, and ethanol).
d) CASE REPORT: Following the ingestion of 53 tablets of colchicine, 500 mcg each, over a 24 to 48 hour period, a 41-year-old man presented to the emergency department with diarrhea and vomiting. Shortly after arrival, the patient had a cardiac arrest with full recovery after 2 minutes of CPR. He subsequently had 2 more cardiac arrests with recovery while in the ED. A profound metabolic acidosis was reported and the patient remained cardiovascularly unstable and died 11 hours after admission (Maxwell et al, 2002).
e) CASE REPORT: A 37-year-old woman became comatose and developed hypotension, bradycardia, cyanosis, and dyspnea, necessitating intubation and mechanical ventilation, approximately 30 hours after intentionally ingesting 38 1-mg colchicine tablets. Cardiac arrest occurred approximately 36 hours post-ingestion. Despite cardiopulmonary resuscitative efforts, the patient died (Aghabiklooei et al, 2014).

a) Hypotension may occur during the early phase of toxicity due to loss of fluid into the extravascular space (Clevenger et al, 1991; McIntyre et al, 1994; Baud et al, 1995; Blackham et al, 2007; Harris et al, 2000). Later hypotension may develop secondary to decreased myocardial contractility or sepsis and may be refractory to fluid resuscitation and vasopressor infusions (Aghabiklooei et al, 2014; Baud et al, 1995; Goldbart et al, 2000; Mullins et al, 2000; Mullins et al, 2000a; Hung et al, 2001; Maxwell et al, 2002). Early monitoring for serum troponin I and echocardiography may alert the clinician to impending cardiovascular collapse (Mullins et al, 2000a).
b) CASE REPORT: A 3-year-old girl developed vomiting, tachycardia (160 bpm) and persistent hypotension (80/60 mmHg) after ingesting 20 colchicine tablets (0.7 mg/kg). The hypotension gradually resolved following aggressive fluid replacement and vasopressor therapy (Bicer et al, 2007).
c) Acute circulatory insufficiency within 72 hours is associated with a high mortality. Death may be due to dysrhythmias and cardiovascular collapse (Sauder et al, 1983; Mullins et al, 2000a).
d) CASE REPORT: A 22-year-old woman presented to the emergency department with nausea, vomiting, diarrhea, and abdominal pain after ingesting 24 0.5-mg colchicine tablets. Physical exam showed hypotension (60/40 mmHg) and sinus tachycardia (114 bpm), and laboratory analysis revealed elevated liver enzymes and creatine kinase concentrations. She recovered with supportive care (Altiparmak et al, 2002).

a) Tachycardia may develop during the early phase of toxicity secondary to volume loss (Huang et al, 2007; Blackham et al, 2007; Bicer et al, 2007; Maxwell et al, 2002; Harris et al, 2000; Baud et al, 1995; McIntyre et al, 1994).
b) CASE REPORT: A 22-year-old woman presented to the emergency department with nausea, vomiting, diarrhea, and abdominal pain after ingesting 24 0.5-mg colchicine tablets. Physical exam showed hypotension (60/40 mmHg) and sinus tachycardia (114 bpm), and laboratory analysis revealed elevated liver enzymes and creatine kinase concentrations. She recovered with supportive care (Altiparmak et al, 2002).

a) Bradycardia may develop during the second phase secondary to myocardial injury (Harris & Gillett, 1998).
b) CASE REPORT: Severe bradycardia occurred in a 37-year-old woman approximately 30 hours after intentionally ingesting 38 1-mg colchicine tablets (Aghabiklooei et al, 2014).

a) Pure motor neuropathy and myopathy leading to profound weakness can progress to respiratory insufficiency (Neuss et al, 1986).

a) Respiratory arrest may result from an ascending paralysis occurring more than 4 hours post exposure (Murray et al, 1983).

a) Severe cases of colchicine toxicity may result in adult respiratory distress syndrome (ARDS), which generally occurs in the second stage of poisoning (24 hours or more after ingestion) (Milne & Meek, 1998; Kubler, 2000; Weakley-Jones et al, 2001).
b) CASE REPORT: Bilateral diffuse parenchymal infiltrates compatible with adult respiratory distress syndrome have been reported (Heaney et al, 1976).
c) CASE REPORT: Two cases of ARDS occurred between 24 and 72 hours postingestion. Postmortem examination was consistent with this diagnosis (Maurizi et al, 1986).
d) Baud et al (1992) also reported ARDS as an effect of poisoning.
e) CASE REPORT: Respiratory failure with the development of aspiration pneumonia and ARDS was reported in a 39-year-old woman. She received supportive care and recovered without sequelae (Berlin et al, 1997).
f) CASE REPORT: A 10-year-old boy presented with severe nausea and vomiting approximately 4 hours after intentionally ingesting 30 1-mg colchicine tablets. Despite aggressive decontamination, including multiple doses of activated charcoal, the patient developed tachycardia, hypotension, fever, epigastric tenderness, hematuria, and severe tachypnea, requiring intubation. An ECG indicated non-specific T-wave changes. Continuous renal replacement therapy was initiated 26 hours post-ingestion and continued for 20 hours; however, the patient subsequently developed upper gastrointestinal hemorrhage, thrombocytopenia, and rhabdomyolysis, unresponsive to supportive therapy, including vitamin K, fresh frozen plasma, and platelet administration. Three days post-ingestion, the patient continued to deteriorate clinically, developing icter, severe agitation, pre-orbital edema, eyelash ecchymosis, and bleeding from his IV sites, with subsequent death due to acute respiratory distress syndrome and disseminated intravascular coagulopathy (Aghabiklooei et al, 2014).

a) Epithelial cell mitotic arrest in otherwise normal cells of the esophagus and bronchioles is a feature characteristic of colchicine toxicity. This has been a useful postmortem histologic marker (Gilbert & Byard, 2002; Weakley-Jones et al, 2001).

a) CASE REPORT: A 73-year-old man developed renal and respiratory failure and subsequently died approximately 18 hours after receiving a 1 mg dose of colchicine IV. He had also been taking 0.6 mg of colchicine orally daily for 8 days prior to receiving IV colchicine (Jones et al, 2002).

a) CASE REPORT: A 12-year-old girl, receiving colchicine therapy for treatment of familial Mediterranean fever, presented to the ED with diarrhea, vomiting, and abdominal pain. Physical examination was consistent with signs of dehydration. Interview of the patient's family indicated a suspected ingestion of approximately 35 colchicine tablets (17 mg [0.48 mg/kg]) approximately 11 hours before presentation. Despite administration of IV fluids, her condition worsened and she was intubated and mechanically ventilated due to respiratory failure. Within a few hours, she developed decompensated shock and treatment with IV dopamine, epinephrine, and norepinephrine was initiated, with an increase in doses as her circulation worsened. However, her condition continued to deteriorate with non-palpable pulses, pulmonary edema, anuria, metabolic acidosis, and impairment of cardiac contractions with an ejection fraction of 40%. Despite continued aggressive supportive therapies, she died approximately 29 hours post-ingestion (Vatansever et al, 2015).

a) Toxic doses produce mental confusion, loss of deep tendon reflexes and ascending paralysis (Nadius et al, 1977; Carr, 1965). Peripheral neuropathy and ascending paralysis may occur during the second phase of poisoning, up to 7 days after ingestion (Maxwell et al, 2002).

a) Seizures may occur following overdose (Carr, 1965; Simons & Kingma, 1989; Heaney et al, 1976) and are usually seen in the second phase of poisoning, up to 7 days after ingestion (Maxwell et al, 2002). This can also result in respiratory failure (Wallace, 1974).
b) A left-sided focal seizure secondary to hyponatremia occurred in a 3-year-old child 7 days after ingesting 20 colchicine tablets (0.7 mg/kg) (Bicer et al, 2007).

a) Numbness in fingers and toes has also been reported at lower doses (1 to 1.5 mg/day) (Van Der Naalt et al, 1992).

a) CASE REPORT: Tingling and numbness in the fingers occurred in a 59-year-old man following a multiple drug overdose including 30 to 40 mg of colchicine (Wells et al, 1989).

a) CASE REPORT: A neuromyopathy characterized by progressive muscular weakness and distal motor and sensory neuropathy has been reported in patients with chronic renal insufficiency after conventional doses (Altiparmak et al, 2002; Van Der Naalt et al, 1992).

a) Peripheral neuropathy has occurred in both human and animal poisonings (Baud et al, 1995). Peripheral neuropathy and ascending paralysis may occur, usually during the second phase of poisoning, up to 7 days after ingestion (Maxwell et al, 2002). Myelin degeneration has been seen at autopsy (Carr, 1965; Brown & Seed, 1945; Stapczynski et al, 1981).

a) Agitation may be seen in overdose (Aghabiklooei et al, 2014; Clevenger et al, 1991).

a) Disorientation has been seen following overdose in an adult and a young child (Berlin et al, 1997; Guven et al, 2002).

a) CASE REPORT: Acute congestion and edema of the brain were observed on autopsy following overdose in one case (Heaney et al, 1976).

a) CASE REPORT: An adult ingested 54 mg of colchicine and developed encephalopathy, respiratory failure, and pancytopenia 3 days following exposure. The patient responded to G-CSF (granulocyte-colony stimulating factor) and supportive care and was discharged without sequelae on day 14 (Berlin et al, 1997).

a) CNS depression progressing to coma may develop following overdose (Aghabiklooei et al, 2014; Clevenger et al, 1991).

a) Nausea, vomiting, severe diarrhea, and hemorrhagic gastroenteritis commonly occur 2 to 12 hours post ingestion and result in loss of fluids and electrolytes (Vatansever et al, 2015; Aghabiklooei et al, 2014; Blackham et al, 2007; Huang et al, 2007; Gilbert & Byard, 2002; Iacobuzio-Donahue et al, 2001; Kubler, 2000; Berlin et al, 1997; Critchley et al, 1997; Baud et al, 1992; Van Der Naalt et al, 1992; Katz et al, 1992; McIntyre et al, 1994; Folpini & Furfori, 1995).
b) Severe dehydration and shock may develop.
c) Colchicine is capable of producing the GI effects even when injected.
d) CASE REPORT: Nausea, vomiting, abdominal pain, and diarrhea occurred in a 22-year-old woman who ingested 24 0.5-mg colchicine tablets (Altiparmak et al, 2002).
e) CASE REPORT: A 26-year-old woman developed profuse diarrhea and abdominal tenderness within 24 hours after intentionally ingesting 27.5 mg colchicine, as well as 600 mg famotidine and 5 g paracetamol. The patient recovered with supportive care (Kocak et al, 2008).
f) A 91.5 kg adolescent girl presented to the hospital with nausea, vomiting, and profuse diarrhea a day after intentionally ingesting a "handful" of her father's colchicine tablets. Investigation of the prescription bottle revealed that she potentially had a maximum ingestion of up to 43 0.5 mg tablets (0.24 mg/kg). With supportive care, she recovered and was discharged 6 days later without sequelae (Gresham et al, 2013).

a) A "burning" sensation of the throat and skin are also prominent symptoms.

a) Toxic ileus may develop following overdose (Heaney et al, 1976; Bruns, 1968).

a) Colchicine is thought to have no specific vascular-damaging properties; the toxic enterocolitis is suggested as based on the particular sensitivity of the rapidly regenerating intestinal epithelial cells, rather than on capillary poisoning (Lendle & Dal Ri, 1959). Sepsis may result in part from gastrointestinal mucosal damage.
b) In fatal overdose cases, as well as, nonfatal toxicity, gastrointestinal biopsies revealed histological findings of numerous metaphase mitoses in gastrointestinal and respiratory epithelium, epithelial pseudostratification, loss of epithelial polarity, and frequent apoptoses which are specific of colchicine poisoning (Gilbert & Byard, 2002; Weakley-Jones et al, 2001; Iacobuzio-Donahue et al, 2001). These features appeared most prominent within the duodenum and gastric antrum, with relative sparing of the gastric body. These findings were not seen in patients taking therapeutic colchicine without clinical toxicity (Iacobuzio-Donahue et al, 2001).

a) CASE REPORT: Elevated serum amylase and lipase developed in a case of fatal colchicine overdose (Clevenger et al, 1991).

a) Nausea, vomiting, diarrhea, and abdominal pain have been reported with long-term colchicine therapy (Neuss et al, 1986).

a) Abdominal pain was reported in a 34-year-old woman who intentionally ingested an unknown amount of colchicine and subsequently developed multi-organ failure (Blackham et al, 2007).

a) CASE REPORT: Two months after treatment with oral colchicine 2 mg/day, a patient developed elevated liver enzymes (Ferrannini & Pentimone, 1984).

a) Biochemical evidence of hepatocellular damage including elevated alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase and prolonged PT may develop following overdose (Aghabiklooei et al, 2014; Blackham et al, 2007; Altiparmak et al, 2002; Harris et al, 2000; Murray et al, 1983; Valenzuela et al, 1995; Milne & Meek, 1998; Huang et al, 2007). Acute renal and hepatic failure have been reported following severe overdose (Bruns, 1968; Hung et al, 2001).
b) In colchicine fatalities, autopsies have revealed focal hepatocyte necrosis (Gilbert & Byard, 2002; Weakley-Jones et al, 2001).
c) CASE REPORT: On autopsy of one case, the liver showed extensive narrow bands of mid-zonal necrosis and numerous hepatocytes containing Mallory hyaline. This patient received 9.3 mg of colchicine over 6 days (Stanley et al, 1984).
d) CASE REPORT: Elevated aminotransferase levels were reported in a 36-year-old woman who died after ingesting 30 mg of colchicine, prolixin, ativan and cogentin (Clevenger et al, 1991). Minimal hepatocellular necrosis and centrilobular congestion were noted on autopsy.
e) CASE REPORT: Mildly elevated aminotransferase levels (ALT 61 units/L, AST 173 units/L; normal 35 to 45 units/L) were reported in a 26-year-old woman approximately 3 days after intentionally ingesting 27.5 mg colchicine, 600 mg famotidine, and 5 g paracetamol. With supportive care, her hepatic enzyme levels returned to normal approximately 8 days post-ingestion (Kocak et al, 2008).

a) Hepatomegaly with tenderness and LFT elevations has been reported.

a) CASE REPORT: A 57-year-old man inadvertently ingested 18 mg of colchicine and developed gastrointestinal symptoms (nausea, vomiting, diffuse abdominal pain) along with a CT finding of hepatic portal venous gas and small bowel thickening (likely source was gas penetrating from a bowel injury). Increased liver enzymes (e.g., SGOT, SGPT, and bilirubin) were also reported. A nasogastric tube was placed for decompression with a gradual decrease in pain, and the patient was discharged 9 days after admission with no sequelae (Saksena et al, 2003).

a) CASE REPORT: A 73-year-old man developed renal and respiratory failure and subsequently died approximately 18 hours after receiving a 1 mg dose of colchicine intravenously. He had also been taking 0.6 mg of colchicine orally daily for 8 days prior to receiving IV colchicine (Jones et al, 2002).

a) Acute oliguric renal failure develops in patients with severe toxicity (Borras-Blasco et al, 2005; McIntyre et al, 1994; Baud et al, 1995; Berlin et al, 1997; Hung et al, 2001).
b) Azotemia, proteinuria, myoglobinuria, and hematuria have been reported (Wallace, 1974; Baud et al, 1992; Van Der Naalt et al, 1992).
c) CASE REPORT: A 48-year-old man presented to the emergency department with a 3-day history of diarrhea and oligo/anuria after ingesting more than 20 tablets of colchicine (total dose greater than 10 g). The patient complained of abdominal pain and an ECG indicated sinus tachycardia. Laboratory data revealed a serum creatinine of 6.1 mg/dL, BUN of 41 mg/dL, a serum myoglobin level of 3194.1 mg/L, a creatine kinase level of 740 international units (IU)/L (normal 56 to 244 IU/L), a lactate dehydrogenase level of 6076 IU/L (normal 180 to 460 IU/L), and elevated liver enzyme levels. With supportive care, the patient gradually recovered with normalization of serum creatinine and BUN levels (Huang et al, 2007).
d) Acute renal failure was reported in 6 patients who received cumulative IV doses of colchicine (ranging from 5.5 to 19 mg) that exceeded the recommended cumulative maximum dose of 2 to 4 mg during a course of therapy. All 6 patients subsequently died (Bonnel et al, 2002).

a) Significant metabolic acidosis may develop with severe poisoning (Vatansever et al, 2015; Aghabiklooei et al, 2014; Murray et al, 1983; Nagy et al, 1994; Milne & Meek, 1998; Kubler, 2000; Hung et al, 2001; Maxwell et al, 2002; Blackham et al, 2007).
b) CASE REPORT: Profound metabolic acidosis (pH 7.0, and HCO3 11.5) was reported in a 41-year-old man following the ingestion of 53 x 500 mcg tablets of colchicine. The patient died within 11 hours of admission with worsening acidosis, circulatory failure and anuria (Maxwell et al, 2002).

a) Rarely, colchicine toxicity with pancytopenia may occur following therapeutic use. This may be seen in patients with risk factors, such as renal insufficiency, hepatic dysfunction, drug interactions, and intravenous colchicine use (Yoon, 2001).

a) In response to the antimitotic effect of colchicine, significant bone marrow depression may occur on the 4th or 5th day following exposure; leukopenia, anemia and thrombocytopenia may be seen (Aghabiklooei et al, 2014; Hung et al, 2001; Maxwell et al, 2002; Guven et al, 2002; Wallace, 1974; Katz et al, 1992; Nagy et al, 1994; McIntyre et al, 1994; Folpini & Furfori, 1995; Valenzuela et al, 1995; Berlin et al, 1997; Critchley et al, 1997; Milne & Meek, 1998; Goldbart et al, 2000).
b) CASE REPORT: Four days after ingesting approximately 30 to 40 mg of colchicine, a 19-year-old developed severe pancytopenia (Katz et al, 1992).
c) CASE REPORT: Three days after ingesting 54 mg of colchicine a 39-year-old woman developed pancytopenia; care was supportive and included G-CSF (granulocyte colony stimulating factor) (Berlin et al, 1997).
d) CASE REPORT: Pancytopenia, with a platelet count of 53 and neutrophil count of 0.2 x 10(9)/L, was reported in a 34-year-old woman following intentional ingestion of an unknown amount of colchicine. The patient had also developed metabolic acidosis and acute hepatic/renal failure. With aggressive supportive therapy, the patient survived (Blackham et al, 2007).
e) CASE REPORT: Leukopenia, thrombocytopenia, and anemia developed in a 3-year-old girl within 3 days after ingesting 20 colchicine tablets (0.7 mg/kg). The pancytopenia resolved following supportive care, including filgrastim (G-CSF) therapy and transfusions of packed red blood cells and platelets (Bicer et al, 2007).
f) CASE SERIES - Three patients developed leukopenia and thrombocytopenia approximately 3 to 4 days after overdose ingestions (ranging from 20 to 48 mg) of colchicine. All 3 patients recovered following treatment with G-CSF (Harris et al, 2000).
g) CASE SERIES: Sixteen of 20 patients (80%) who died following IV administration of colchicine developed significant myelosuppression prior to death. Colchicine doses that were administered ranged from 5.5 to 19 mg, exceeding the cumulative maximum dose of 2 to 4 mg recommended during a course of therapy (Bonnel et al, 2002).
h) CASE REPORT: A 26-year-old woman presented to the emergency department with abdominal pain and fever (36.7 degrees C) approximately 1.5 hours after intentionally ingesting 27.5 mg colchicine, 600 mg famotidine, and 5 g paracetamol. At admission her laboratory values were unremarkable except for a white blood cell (WBC) count of 34.1 x 10(3)/mcL (normal 4 to 10 x 10(3)/mcL), a hemoglobin level of 14.7 g/dL (normal 12 to 14 g/dL), and a platelet count of 207 x 10(3)/mcL (normal 150 to 400 x 10(3)/mcL). Three days later, a repeat laboratory analysis revealed a decrease in WBC and platelet counts and hemoglobin levels (4.8 x 10(3)/mcL, 31 x 10(3)/mcL, and 10.5 g/dL, respectively). She subsequently developed pneumonia and vaginal candidiasis, but she made a complete recovery following antibiotic therapy (Kocak et al, 2008).
i) CASE REPORT: A 25-year-old woman presented with vomiting approximately 4 hours after intentionally ingesting 25 1-mg colchicine tablets. Following administration of multiple doses of activated charcoal and 24 hours of observation, the patient was discharged without developing signs or symptoms of severe toxicity. Approximately 5 days later, the patient presented with severe back pain and thrombocytopenia (platelet count: 59,000). Three days post-admission, following administration of platelets, laboratory data revealed a white blood cell count of 2300, which increased to 5200 following administration of granulocyte colony stimulating factors. With supportive therapy, the patient continued to improve and was discharged 5 days later (Aghabiklooei et al, 2014).

a) Heinz body hemolytic anemia has also been reported following overdose (Heaney et al, 1976).

a) A consumptive coagulopathy with prolongation of coagulation times, a decrease in fibrinogen, elevated fibrin degradation products and thrombocytopenia has been reported (Bismuth et al, 1977; Ferrannini & Pentimone, 1984).
b) CASE REPORT: A 69-year-old man receiving 9.3 mg over 6 days developed severe toxicity, including clinical and laboratory features of DIC.
c) In vitro platelet aggregation and platelet adhesiveness are reduced and may contribute to bleeding (Soppitt & Mitchell, 1969). The etiology of DIC is probably multifactorial.
d) CASE REPORT: A 70-year-old man receiving colchicine for treatment of gout had thrombocytopenia in the presence of increased megakaryocytes in the bone marrow, suggesting his cause of thrombocytopenia was not due to marrow failure. Other references to colchicine-induced thrombocytopenia site the antimitotic effects of colchicine on the marrow as the cause in decreased number of platelets. In this case increased platelet destruction was the cause and antiplatelet antibodies were negative (Vedia et al, 1993).

a) Prolonged prothrombin time and activated partial thromboplastin time may develop (Aghabiklooei et al, 2014; Bicer et al, 2007; Baud et al, 1995; Folpini & Furfori, 1995; Murray et al, 1983; McIntyre et al, 1994).

a) Marked elevations in the white blood cell count are common early in the course of intoxication due to significant volume depletion (Vatansever et al, 2015; Kocak et al, 2008; Kubler, 2000; Nagy et al, 1994; Baud et al, 1995).
b) A rebound leukocytosis typically follows the initial leukopenia (Folpini & Furfori, 1995; Nadius et al, 1977; Murray et al, 1983). In a pediatric case, a rebound leukocytosis (WBC 23,000/mm(3)), was seen during the second week of hospitalization (Goldbart et al, 2000).

a) CASE REPORT: Two months after starting low-dose colchicine therapy, a patient developed transient but profound granulocytopenia; it reversed 4 days after the drug was discontinued (Finklestein et al, 1987).
b) CASE REPORT - Several days after an increase in an adult's colchicine dose to 0.6 mg every 4 hours, sudden onset of severe neutropenia (absolute neutrophil count of 240 cells/mm(3)) was reported. The WBC count returned to normal after stopping colchicine therapy and administration of filgrastim (Dixon & Wall, 2001).

a) CASE REPORT: A 39-year-old woman developed neutropenia following an intentional ingestion of colchicine (54 mg). Her hospital course was complicated by respiratory failure, encephalopathy, and a febrile state. By day 3, the patient developed coagulopathy, pancytopenia, and electrolyte abnormalities (Berlin et al, 1997).
b) CASE REPORT: A 43-year-old woman ingested 25-30 mg of colchicine and initially developed gastrointestinal disturbances followed by pancytopenia and neutropenia within 72 hours following exposure. She was successfully treated with two doses of G-CSF (total dose 600 mcg SC) to stimulate bone marrow function; WBC dramatically increased following G-CSF. The patient's WBC was within normal limits within three weeks (Critchley et al, 1997).
c) CASE REPORT: A 25-year-old woman presented with vomiting approximately 4 hours after intentionally ingesting 25 1-mg colchicine tablets. Following administration of multiple doses of activated charcoal and 24 hours of observation, the patient was discharged without developing signs or symptoms of severe toxicity. Approximately 5 days later, the patient presented with severe back pain and thrombocytopenia (59,000). Three days post-admission, following administration of platelets, laboratory data revealed a white blood cell count of 2300, which increased to 5200 following administration of granulocyte colony stimulating factors. With supportive therapy, the patient continued to improve and was discharged 5 days later (Aghabiklooei et al, 2014).

a) CASE REPORT: Large, darkly staining, intracytoplasmic inclusions were noted in the neutrophils of a patient following an overdose of colchicine; polymorphonuclear neutrophils also contained intracytoplasmic and intranuclear vacuoles (Powell & Wolf, 1976).

a) Severe overdoses may result in DIC at the second stage of poisoning (24 hours or more after ingestion) (Bicer et al, 2007; Weakley-Jones et al, 2001).
b) Disseminated intravascular coagulation, with subsequent death, occurred in 4 patients who received IV colchicine in cumulative doses ranging from 5.5 to 19 mg, which exceeds the recommended cumulative maximum dose of 2 to 4 mg (Bonnel et al, 2002).
c) CASE REPORT: A 10-year-old boy presented with severe nausea and vomiting approximately 4 hours after intentionally ingesting 30 1-mg colchicine tablets. Despite aggressive decontamination, including multiple doses of activated charcoal, the patient developed tachycardia, hypotension, fever, epigastric tenderness, hematuria, and severe tachypnea, requiring intubation. An ECG indicated non-specific T-wave changes. Continuous renal replacement therapy was initiated 26 hours post-ingestion and continued for 20 hours; however, the patient subsequently developed upper gastrointestinal hemorrhage, thrombocytopenia, and rhabdomyolysis, unresponsive to supportive therapy, including vitamin K, fresh frozen plasma, and platelet administration. Three days post-ingestion, the patient continued to deteriorate clinically, developing icter, severe agitation, pre-orbital edema, eyelash ecchymosis, and bleeding from his IV sites, with subsequent death due to acute respiratory distress syndrome and disseminated intravascular coagulopathy (Aghabiklooei et al, 2014).

a) CASE REPORT: A 25-year-old woman developed extensive bruising over all 4 extremities after ingesting an unknown amount of colchicine along with indomethacin, allopurinol, and atenolol. Laboratory analysis revealed elevated hepatic enzyme and urea concentrations, neutropenia, and thrombocytopenia. The patient gradually recovered following G-CSF administration (Harris et al, 2000).

a) Reversible hair loss has been reported, usually developing up to 3 weeks after toxic exposure (Blackham et al, 2007; Bicer et al, 2007; Harris et al, 2000; Goldbart et al, 2000; Guven et al, 2002; Gooneratne, 1966; Nadius et al, 1977; Baud et al, 1995; Folpini & Furfori, 1995; Valenzuela et al, 1995; Berlin et al, 1997; Critchley et al, 1997). Complete scalp baldness and loss of secondary sexual hair occurs over days to weeks, with variable recovery over weeks to months (Harris & Gillett, 1998).
b) CASE REPORT: A 26-year-old woman experienced transient total alopecia approximately 2 weeks after intentionally ingesting 27.5 mg colchicine (Kocak et al, 2008).

a) CASE REPORT: Several days following a colchicine overdose (1.3 to 1.5 mg/kg), a 4-year-old girl developed bullous erythematous skin lesions. A few days later, painful, subcutaneous erythema nodosum-like nodules were noted on her pretibial regions, which were described as Sweet syndrome-like eruptions, with biopsy revealing neutrophilic infiltration. The lesions cleared within 20 days (Guven et al, 2002).

a) CASE REPORT: A fixed drug eruption has been reported, consisting of a dark purplish-red macule on the glans penis of a 31-year-old man 5 hours after taking 2.5 mg of colchicine. On oral challenge with the drug, the eruption was again provoked (Mochida et al, 1996).

a) CASE REPORT: A 32-year-old HIV-positive man presented with toxic epidermal necrolysis after 3 days of oral treatment with colchicine for gout. He was also on several other medications, but it was thought the colchicine was responsible for the toxic epidermal necrolysis (Alfandari et al, 1994).

a) A 48-year-old man developed a toxic epidermal necrolysis-like exanthem (vesiculating erythema) with lethal multiorgan failure after ingesting 18 mg (0.2 mg/kg) of colchicine. The authors suggested that the clinical similarity of TEN and the patient's eruptions may derive from the prevalence of apoptotic keratinocytes in both conditions, but concluded that a distinct histopathology involving both metaphase arrest and apoptosis occurs with colchicine toxicity (Arroyo et al, 2004).

a) A limited number of cases of therapeutic colchicine-induced rhabdomyolysis have been reported, most in conjunction with risk factors, such as renal insufficiency and liver dysfunction. Following discontinuation of colchicine, rhabdomyolysis has been reversible (Boomershine, 2002).
b) CASE REPORT: A 59-year-old patient being treated for gout for one month with colchicine (0.6 mg orally twice daily), developed rhabdomyolysis with a CPK of 6961 U/L that resolved within 8 days after colchicine withdrawal (Dawson & Starkebaum, 1997).

a) Rhabdomyolysis with myoglobinuria and myopathy has been reported after overdose (Aghabiklooei et al, 2014; Van Der Naalt et al, 1992; Katz et al, 1992; Murray et al, 1983; Kontos, 1962; Folpini & Furfori, 1995; Valenzuela et al, 1995; Berlin et al, 1997; Critchley et al, 1997; Milne & Meek, 1998).

a) Colchicine overdoses may result in muscle pain and weakness, which may improve within 2 weeks (Guven et al, 2002).

a) Colchicine myopathy occurs in patients with gout who take customary doses. It presents with proximal weakness, increased serum creatinine kinase, and axonal neuropathy (Altiparmak et al, 2002; Van Der Naalt et al, 1992; Kuncl et al, 1987; Murray et al, 1983; Stahl et al, 1979).
b) CASE REPORT: A 71-year-old woman with mild chronic renal insufficiency began colchicine therapy for gout and developed a myoneuropathy one week later, consisting of ptosis and bifacial palsy. All weakness resolved after colchicine withdrawal (Schiff & Drislane, 1992).
c) CASE REPORT: A 57-year-old man with end-stage renal disease on colchicine therapy for gout for 6 weeks was admitted with profound proximal muscle weakness but normal creatinine kinase levels. After discontinuing colchicine his muscle strength returned to normal within 2 weeks (Cook et al, 1994).

a) Colchicine inhibits release of insulin from beta cells (Boehnert & McGuigan, 1983).

a) CASE REPORT: A 57-year-old man accidentally consumed 10 mg of colchicine within one hour and died approximately 2 days later. At autopsy, bilateral adrenal hemorrhage with destruction of the cortex (Waterhouse-Friderichsen syndrome) was diagnosed as the cause of death (Stringfellow et al, 1993).

a) Following severe poisoning, widespread invasive fungal or bacterial invasion of the aerodigestive tract may occur. Infections complicating severe bone marrow suppression are common. Overwhelming sepsis, a complication of colchicine toxicity, may be a cause of death (Kocak et al, 2008; Iacobuzio-Donahue et al, 2001; Hung et al, 2001).

a) The manufacturer has classified colchicine as FDA pregnancy category C (Prod Info COLCRYS(TM) oral tablets, 2014; Prod Info MITIGARE(TM) oral capsules, 2014).
b) Use during pregnancy only if the potential maternal benefit outweighs the potential fetal risk (Prod Info COLCRYS(TM) oral tablets, 2014; Prod Info MITIGARE(TM) oral capsules, 2014).

a) The colchicine and probenecid combination is contraindicated during pregnancy (Prod Info probenecid colchicine oral tablets, 2009).
b) Prior to using the colchicine and probenecid combination in women of childbearing potential, weigh the anticipated benefits against the potential hazards (Prod Info probenecid colchicine oral tablets, 2009).

a) Fetal deaths were reported in animals treated with colchicine. Changes in the live birth and viability index, cytological changes (including somatic cell genetic material), and specific developmental abnormalities in the urogenital system and craniofacial area (including nose and tongue) were observed in offspring (RTECS , 1996).

a) Published developmental and reproduction animal studies indicate that colchicine causes embryofetal toxicity and interrupted postnatal development when given within or above the normal therapeutic range (Prod Info COLCRYS(TM) oral tablets, 2014).
b) Colchicine induced post-implantation mortality and pre-implantation mortality in animals. Other maternal effects, as well as toxic effects, on fertility occurred (RTECS , 1996).
c) In another study, when female animals were dosed with colchicine 3 hours prior to ovulation, 26% of the first-cleavage embryos were polyploid. In those dosed 12 hours prior to ovulation, 100% were polyploid (Albanese, 1988).

a) In a study assessing the prognostic factors of acute colchicine ingestion, patients with the highest WBC in the first three days after admission had better prognoses. The study emphasizes the importance of careful CBC monitoring during the days after ingestion (Baud et al, 1995).

a) In a study assessing the prognostic factors of acute colchicine ingestion, patients with the lowest prothrombin time in the first three days after admission had better prognoses. The study emphasizes the importance of careful monitoring of prothrombin time during the days after ingestion (Baud et al, 1995).

a) Monitor ECG for cardiac dysrhythmias.

a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
b) ADVERSE EFFECTS/CONTRAINDICATIONS

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
b) ADVERSE EFFECTS/CONTRAINDICATIONS

a) Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.

a) SEIZURE CONTROL: Is mandatory prior to gastric lavage.
b) AIRWAY PROTECTION: Place patients in the head down left lateral decubitus position, with suction available. Patients with depressed mental status should be intubated with a cuffed endotracheal tube prior to lavage.

a) Use small aliquots of liquid. Lavage with 200 to 300 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in older children or adults) and 10 milliliters/kilogram body weight of normal saline in young children(Vale et al, 2004) and repeat until lavage return is clear.
b) The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
c) CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.

a) Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications (Caravati et al, 2001).
b) Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).

a) Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.

a) ADULT DOSE: Optimal dose not established. After an initial dose of 50 to 100 grams of activated charcoal, subsequent doses may be administered every 1, 2 or 4 hours at a dose equivalent to 12.5 grams/hour (Vale et al, 1999), do not exceed: 0.5 g/kg charcoal every 2 hours (Ghannoum & Gosselin, 2013; Mauro et al, 1994). There is some evidence that smaller more frequent doses are more effective at enhancing drug elimination than larger less frequent doses (Park et al, 1983; Ilkhanipour et al, 1992). PEDIATRIC DOSE: Optimal dose not established. After an initial dose of 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) (Chyka & Seger, 1997), subsequent doses may be administered every 1, 2 or 4 hours (Vale et al, 1999) in a dose equivalent to 6.25 grams/hour in children 1 to 12 years old.
b) Activated charcoal should be continued until the patient's clinical and laboratory parameters, including drug concentrations if available, are improving (Vale et al, 1999). The patient should be frequently assessed for the ability to protect the airway and evidence of decreased peristalsis or intestinal obstruction.
c) Use of cathartics has not been shown to increase drug elimination and may increase the likelihood of vomiting. Routine coadministration of a cathartic is NOT recommended (Vale et al, 1999).
d) AGENTS AMENABLE TO MDAC THERAPY: The following properties of a drug that are likely to allow MDAC therapy to be effective include: small volume of distribution, low protein binding, prolonged half-life, low intrinsic clearance, and a nonionized state at physiologic pH (Chyka, 1995; Ghannoum & Gosselin, 2013).
e) Vomiting is a common adverse effect; antiemetics may be necessary.
f) CONTRAINDICATIONS: Absolute contraindications include an unprotected airway, intestinal obstruction, a gastrointestinal tract that is not intact and agents that may increase the risk of aspiration (eg, hydrocarbons). Relative contraindications include decreased peristalsis (eg, decreased bowel sounds, abdominal distention, ileus, severe constipation) (Vale et al, 1999; Mauro et al, 1994).
g) COMPLICATIONS: Include constipation, intestinal bleeding, bowel obstruction, appendicitis, charcoal bezoars, and aspiration which may be complicated by acute respiratory failure, adult respiratory distress syndrome or bronchiolitis obliterans (Ghannoum & Gosselin, 2013; Ray et al, 1988; Atkinson et al, 1992; Gomez et al, 1994; Mizutani et al, 1991; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Mina et al, 2002; Harsch, 1986; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002).

a) Ondansetron (0.14 milligrams/kilogram) was successfully used to prevent vomiting after administration of activated charcoal in a 16-year-old girl with colchicine overdose (Reed & Marx, 1994).

a) Treatment is supportive with attention to the airway, breathing, and circulation. For mild to moderate overdose, consider GI decontamination and treat for shock. Administer IV fluids, antiemetics, and pressors if needed.

a) Treatment is supportive in the ICU. Multiorgan system failure may occur 1 to 7 days post-ingestion. Treat with IV fluids, vasopressors, cardiac monitoring, intubation, antibiotics for sepsis, dialysis for acute renal failure as needed. Pancytopenia has been reported. For severe neutropenia, administer colony stimulating factor (e.g., filgrastim, sargramostim). If severe coagulopathy with bleeding develops transfuse with RBCs, platelets and fresh frozen plasma as indicated. Treat seizures with IV benzodiazepines or barbiturates.

a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.

a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).

a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
b) DOSE

a) DOSE: ADULT: Infuse at 5 to 10 micrograms/kilogram/minute IV. PEDIATRIC: Infuse at 2 to 20 micrograms/kilogram/minute IV or intraosseous, titrated to desired effect (Peberdy et al, 2010; Kleinman et al, 2010).
b) CAUTION: Decrease infusion rate if ventricular ectopy develops (Prod Info dobutamine HCl 5% dextrose intravenous injection, 2012).

a) Filgrastim: The usual starting dose in adults is 5 micrograms/kilogram/day by intravenous infusion or subcutaneous injection (Prod Info NEUPOGEN(R) injection, 2006).
b) Sargramostim: Usual dose is 250 micrograms/square meter/day infused IV over 4 hours (Prod Info LEUKINE(R) injection, 2006).
c) Monitor CBC with differential.

a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).

a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):

a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)

a) HUMAN DATA: A 25-year-old woman developed hypotension refractory to pressors, decreased cardiac index, oliguria and ARDS after ingesting 60 milligrams of colchicine, 900 milligrams of phenobarbital and 750 milligrams of opium extract (Baud et al, 1995).
b) ANIMAL DATA
c) TISSUE STUDY

a) In a mouse model of colchicine toxicity, treatment with aspartic acid the day prior to colchicine administration increased survival (Wang et al, 1993). Treatment with aspartic acid the day of colchicine administration had no effect on survival and aspartic acid treatment after colchicine administration decreased survivals. No effect was observed after treatment with glutamic acid using any of the dosing schedules.

a) Therapeutic serum colchicine range after a 1 milligram oral dose is reported to be 3 to 5 nanograms/milliliter at 0.5 to 2 hours after dosing (Mullins et al, 2000).

a) Postmortem blood levels of 0.3 to 0.4 micromoles/liter were found in a 28-year-old man who died after massive colchicine ingestion (Davies et al, 1988).
b) The toxic effects of colchicine have been associated with blood levels greater than 5 micrograms/liter (Van Der Naalt et al, 1992).
c) A 30-year-old male died due to cardiovascular collapse about 35 hours following a colchicine overdose of 39.6 milligrams (0.40 milligrams/kilogram). Serum colchicine concentration reported 13 hours before death (approximately 22 hours after ingestion) was 29 nanograms/milliliter (Mullins et al, 2000).
d) Postmortem fluid and tissue colchicine concentrations of a 73-year-old man, who developed renal and respiratory failure and died after receiving a 1 mg IV dose of colchicine and after taking 0.6 mg of oral colchicine daily for eight days, are as follows (Jones et al, 2002):

a) 1197 mcg/kg

a) 2 mg/kg

a) 5886 mcg/kg
b) 66.6 mg/kg

a) 1200 mcg/kg

a) 6100 mcg/kg
b) 3300 mcg/kg