a) EARLY PHASE (0 to 24 hours): Consists of severe gastrointestinal symptoms (ie, nausea, vomiting, abdominal pain, hemorrhagic gastroenteritis) with resulting electrolyte abnormalities, volume depletion, and hypotension.
b) SECOND PHASE (1 to 7 days): Multiorgan system failure: Possible risk of sudden cardiac death, dysrhythmias, confusion, coma, seizures, pancytopenia, renal failure, hepatic failure, sepsis, ARDS, electrolyte imbalances, and rhabdomyolysis.
c) THIRD PHASE (over 7 days): Recovery or death: Alopecia, myopathy, neuropathy, or myoneuropathy, rebound leukocytosis, death is usually caused by respiratory failure, intractable shock, dysrhythmias, and cardiovascular collapse.

a) Transient liver elevations in transaminase levels have been reported (Boisrame-Helms et al, 2015; Brvar et al, 2004; Flesch et al, 2002; Danel et al, 2001; Mendis, 1989).
b) Elevated blood levels of hepatic enzymes has been reported two days after the accidental, ultimately fatal, ingestion of Colchicum autumnale (meadow saffron). Postmortem examination showed enlarged liver and spleen, and significant hemorrhagic necrosis around central hepatic veins. Hepatocytes revealed hydropic or microvesicular fatty change, and portal triads were sparely infiltrated by mononuclei (Sundov et al, 2005).
c) CASE REPORT: Elevated liver enzyme levels were reported in a 43-year-old woman 2 days after unintentionally ingesting Colchicum autumnale. Viral hepatitis markers were negative and an abdominal ultrasonography was normal. Her liver enzyme levels gradually normalized within 18 days post ingestion (Gabrscek et al, 2004).

a) Severe poisonings have resulted in liver failure. In one fatality, autopsy revealed widespread hepatic necrotic changes (Brncic et al, 2001).

a) Hyperbilirubinemia (total bilirubin 50.7 mcmol/L; normal 1.7-20.5 mcmol/L) has been reported two days after the accidental ingestion of Colchicum autumnale (meadow saffron) (Sundov et al, 2005).

a) Oliguria or anuria secondary to volume depletion is common (van Zoelen et al, 2002; Mendis, 1989; Nagaratnam et al, 1973). In one fatality, autopsy revealed widespread renal necrotic changes (Brncic et al, 2001).
b) Elevated blood urea nitrogen (18.1 mmol/L; normal 2.5-8.3 mmol/L) and creatinine (295 mcmol/L; normal 54.2 to 116.0 mcmol/L) have been reported two days after the accidental, ultimately fatal, ingestion of Colchicum autumnale (meadow saffron). Postmortem examination of the patient revealed acute tubular necrosis without myoglobin or other casts in the kidneys (Sundov et al, 2005).
c) CASE REPORT: A 76-year-old man developed anuria approximately 4 days after unintentionally ingesting 2 whole plants of Colchicum autumnale. Laboratory data revealed a peak serum creatinine level of 524 mcmol/L (normal value less than 133 mcmol/L). The patient's clinical condition continued to deteriorate, resulting in fatal cardiac arrest approximately 3 days post ingestion. An autopsy revealed kidney necrosis (Brvar et al, 2004a).
d) CASE REPORT: A 43-year-old woman developed renal insufficiency following unintentional ingestion of Colchicum autumnale. Laboratory findings, obtained approximately 2 days post ingestion, showed a serum creatinine level of 224 mcmol/L (normal 44 to 97 mcmol/L) and a urea level of 20.4 mmol/L (normal 2.8 to 7.5 mmol/L). Her laboratory values normalized with supportive care; however, on hospital day 6 (approximately 8 days post ingestion), she developed tubular dysfunction with proteinuria initially, hyponatremia (122 mmol/L {normal 135 to 145 mmol/L}), hypophosphatemia (0.67 mmol/L {normal 0.80 to 1.4 mmol/L}), and polyuria. The patient gradually recovered and was discharged on hospital day 17 (approximately 19 days post ingestion) (Gabrscek et al, 2004).

a) Proteinuria and mild hematuria have been reported after ingestion of plants containing colchicine alkaloids (Brncic et al, 2001; Mendis, 1989).

a) INCIDENCE: In a series of 49 patients with Gloriosa superba intoxication, 1 (2%) developed fever (Fernando & Fernando, 1990).

a) Hypotension has been reported in children after ingestion of Gloriosa superba (Aleem, 1992). It may be due to loss of fluid into the extravascular space and possibly contributory direct myocardial toxicity. Hypotension has also been reported in adults within 3 days following a toxic ingestion of plants containing colchicine alkaloids (Flesch et al, 2002; van Zoelen et al, 2002; Brncic et al, 2001).
b) Hypotension has been reported two days after the accidental ingestion of Colchicum autumnale (meadow saffron) (Sundov et al, 2005).
c) Hypotension, unresponsive to hydration and norepinephrine administration, occurred in a 76-year-old man who unintentionally ingested Colchicum autumnale. The patient's clinical condition continued to deteriorate, resulting in fatal cardiac arrest 3 days post-ingestion (Brvar et al, 2004a).

a) Reflex tachycardia is also common (van Zoelen et al, 2002; Brncic et al, 2001; Naidus et al, 1977; Nagaratnam et al, 1973; Gooneratne, 1966).
b) Tachycardia has been reported two days after the accidental ingestion of Colchicum autumnale (meadow saffron) (Sundov et al, 2005).
c) Sinus tachycardia (122 bpm) was reported in a 76-year-old man who unintentionally ingested 2 whole plants of Colchicum autumnale (Brvar et al, 2004a).

a) Severe acidosis, refractory to sodium bicarbonate infusions, has been reported in severe cases (Brvar et al, 2004a; van Zoelen et al, 2002; Brncic et al, 2001).

a) In response to the antimitotic effect of colchicine, bone marrow depression may occur on the 3rd or 4th day following exposure; anemia, leukopenia and thrombocytopenia may occur (Premaratna et al, 2015; Boisrame-Helms et al, 2015; Sundov et al, 2005; Brvar et al, 2004; Gabrscek et al, 2004; Flesch et al, 2002; Brncic et al, 2001; Mendis, 1989).
b) Polymicrobial infection may result.

a) Elevated prothrombin time and activated partial thromboplastin time may develop.
b) CASE REPORT: A 29-year-old man developed anemia, thrombocytopenia, leukopenia, a prolonged prothrombin time, bleeding time and clotting time 5 days after ingesting tubers of Gloriosa superba (Mendis, 1989).
c) Prolonged prothrombin time and thrombocytopenia (platelets 10 x 10(9)/L; normal 130-400 x 10(9)/L) have been reported two days after the accidental ingestion of Colchicum autumnale (meadow saffron) (Sundov et al, 2005)
d) CASE REPORT: An elevated INR (1.9; normal 1.2), anemia (3.3 x 10(12)/L; normal 4.15 to 4.90 x 10(12)/L), and thrombocytopenia (51 x 10(9)/L; normal 130 to 400 x 10(9)/L) were reported in a 76-year-old man who unintentionally ingested 2 whole Colchicum autumnale plants. The patient's clinical condition continued to deteriorate, with the development of multi-organ failure, resulting in fatal cardiac arrest. An autopsy revealed hypocellular bone marrow with diserythropoiesis, dismyeloiesis, and dismegacaryopoiesis (Brvar et al, 2004a).

a) Patients surviving the second phase of poisoning (multi-organ failure), often develop leukocytosis accompanying recovery (Brvar et al, 2004; van Zoelen et al, 2002).

a) Leukocytopenia (leukocytes 0.7 x 10(9)/L; normal 4-10 x 10(9)/L) has been reported two days after the accidental ingestion of Colchicum autumnale (meadow saffron) (Sundov et al, 2005)

a) Alopecia, accompanying the recovery stage, usually develops 2 to 3 weeks post ingestion with eventual regrowth of hair (Boisrame-Helms et al, 2015; Gooneratne et al, 2014; Brvar et al, 2004; Flesch et al, 2002; van Zoelen et al, 2002; Gooneratne, 1966). In one case, alopecia developed 5 days post ingestion and persisted for 15 days (Flesch et al, 2002). In another case, total alopecia occurred within 14 days in a young adult following intentional ingestion of two tubers of Gloriosa superba; partial regrowth was noted one month after exposure (Premaratna et al, 2015).
b) CASE REPORT: A 43-year-old woman experienced total alopecia approximately 5 days after unintentionally ingesting Colchicum autumnale. During this time, the patient also developed myelosuppression, acute renal failure, and elevated hepatic enzyme levels. After 3 years post ingestion, the patient continued to experience intermittent episodes of hair loss, despite resolution of her other signs and symptoms of acute colchicine poisoning (Gabrscek et al, 2004).

a) Increase in creatine kinase (CK) is consistent with colchicine poisoning (Boisrame-Helms et al, 2015; Flesch et al, 2002).
b) Elevated creatine kinase (10,120 Units/L; normal 15 to 130 Units/L) has been reported two days after the accidental ingestion of Colchicum autumnale (meadow saffron) (Sundov et al, 2005).
c) CASE REPORT: Elevated creatine kinase and myoglobin levels (19 mckat/L and 3696 mcg/L, respectively) were reported in a 76-year-old man who unintentionally ingested 2 whole plants of Colchicum autumnale. The patient's clinical condition continued to deteriorate, resulting in asystolic cardiac arrest with unsuccessful resuscitation approximately 3 days post ingestion (Brvar et al, 2004a).

a) CASE REPORT: A 43-year-old woman complained of muscle weakness 12 to 24 weeks following unintentional ingestion of Colchicum autumnale. The muscle weakness continued to persist 3 years post ingestion, although her creatine kinase levels were normal (Gabrscek et al, 2004).

a) Low serum glucose levels may occur following toxic plant ingestions (Brncic et al, 2001).

a) Hyperglycemia, lasting for 2 months following colchicine plant poisoning, was reported in one adult case (Flesch et al, 2002).
b) An elevated blood sugar of 280 mg/dL was reported in an adult with colchicine poisoning (Sannohe et al, 2002).

a) An adult developed hypocalcemia about 5 days after intentionally ingesting Gloriosa superba tubers. Serum calcium was 0.9 mmol/L (normal 1.1 to 1.4). Her clinical course was further complicated by seizure activity and neurologic toxicity. Other laboratory studies were within normal limits except for mildly elevated liver enzymes. She gradually improved with anticonvulsant and IV calcium therapy (Gooneratne et al, 2014).

a) Hypotension has been reported in children after ingestion of Gloriosa superba (Aleem, 1992). It may be due to loss of fluid into the extravascular space and possibly contributory direct myocardial toxicity. Hypotension has also been reported in adults within 3 days following a toxic ingestion of plants containing colchicine alkaloids (Flesch et al, 2002; van Zoelen et al, 2002; Brncic et al, 2001).
b) SHOCK: Volume depletion secondary to the severe gastrointestinal symptoms may lead to fatal shock (Nagaratnam et al, 1973). Severe refractory hypotension resulting in cardiovascular collapse and death has been reported in an adult with multiorgan failure due to Colchicum autumnale poisoning (Brncic et al, 2001).
c) Hypotension has been reported two days after the accidental ingestion of Colchicum autumnale (meadow saffron/autumn crocus) (Sundov et al, 2005; Gabrscek et al, 2004).
d) Hypotension, unresponsive to hydration and norepinephrine administration, occurred in a 76-year-old man who unintentionally ingested 2 whole Colchicum autumnale plants. The patient's clinical condition continued to deteriorate, and he died approximately 3 days post ingestion (Brvar et al, 2004a).

a) CASE REPORT: A 68-year-old woman inadvertently ingested C. autumnale mistaking the plant for wild leeks. Several days after exposure, the patient developed severe shock and multi-organ failure and was admitted to an ICU setting. Laboratory studies showed evidence of numerous clinical events including pancytopenia (requiring blood products), acute liver and renal failure, rhabdomyolysis, severe metabolic acidosis, and cardiac failure. A peak colchicine (10 ng/mL; therapeutic range, 0.6 mg/dL) plasma concentration was reached on day 4. Cardiogenic shock was initially treated with dobutamine (10 mcg/kg/min) and close hemodynamic monitoring including Swan-Ganz and echocardiography. A transthoracic echocardiography revealed global hypokinesia with a left ventricular ejection fraction of 5% to 10%, severe right ventricular dysfunction with moderate tricuspid regurgitation. However, despite these efforts hemodynamic instability persisted and the patient was started on extracorporeal life support (ECLS) at a rate of 3.5 L/min and 3800 rev/min. Gradually, her cardiac function improved and ECLS was removed on day 10. Ongoing clinical complications included sudden arrhythmias with third-degree atrioventricular block on day 12 with cardiac arrest that was treated successfully with resuscitation. Persistent renal failure required intermittent hemodialysis until day 23 and mechanical ventilation was needed until day 20. By day 24, the patient had completely recovered from multi-organ failure and was discharged to home with no permanent sequelae (Boisrame-Helms et al, 2015).

a) Severe chest pain associated with ST elevations was seen on days 3 to 5 after ingestion of Gloriosa superba tubers. The patient showed clinical features of acute left ventricular failure (Mendis, 1989).
b) In a case of Colchicum autumnale ingestion, T wave inversion was seen on ECG in an adult (Flesch et al, 2002).
c) CASE REPORT: A prolonged QTc interval (467 ms) was reported in a 43-year-old woman 2 days after unintentionally ingesting Colchicum autumnale (Gabrscek et al, 2004).

a) Reflex tachycardia is also common (van Zoelen et al, 2002; Brncic et al, 2001; Naidus et al, 1977; Nagaratnam et al, 1973; Gooneratne, 1966).
b) Tachycardia has been reported two days after the accidental ingestion of Colchicum autumnale (meadow saffron) (Sundov et al, 2005).
c) CASE REPORT: Episodes of bradycardia and junctional tachycardia were reported in a 71-year-old woman who unintentionally ingested Colchicum autumnale (autumn crocus) (Brvar et al, 2004).
d) CASE REPORT: Sinus tachycardia (122 bpm) was reported in a 76-year-old man who unintentionally ingested 2 whole plants of Colchicum autumnale (Brvar et al, 2004a).

a) Bradycardia has been reported in children after ingestion of Gloriosa superba (Aleem, 1992).
b) CASE REPORT: Episodes of bradycardia and junctional tachycardia were reported in a 71-year-old woman who unintentionally ingested Colchicum autumnale (autumn crocus) (Brvar et al, 2004).

a) In a series of 49 patients with Gloriosa superba intoxication, 8 (16%) developed chest pain (Fernando & Fernando, 1990).

a) CASE REPORT: An echocardiogram showed heart dilatation with an ejection fraction of less than 30% in a 76-year-old man 2 days after he unintentionally ingested 2 whole Colchicum autumnale plants. The ECG revealed diffuse nonspecific ST changes, and troponin I levels were elevated, indicating myocardial necrosis. The patient's clinical condition continued to deteriorate, resulting in fatal cardiac arrest approximately 3 days post-ingestion. An autopsy showed heart dilatation (Brvar et al, 2004a).

a) Acute respiratory failure, requiring intubation and assisted mechanical ventilation, may occur in severe cases (Boisrame-Helms et al, 2015; van Zoelen et al, 2002; Brncic et al, 2001). Respiratory arrest is frequently the terminal event in fatal cases (Nagaratnam et al, 1973).
b) CASE REPORT: A 39-year-old man developed a sudden onset of severe dyspnea and respiratory distress progressing to apnea approximately 30 hours after inadvertently ingesting Colchicum persicum thought to be wild garlic. Despite immediate oxygenation, mechanical ventilation and cardiopulmonary resuscitation, the patient did not respond to resuscitation efforts and died of cardiopulmonary arrest. Postmortem examination showed pulmonary edema and congestion and the plant ingested was confirmed to be C. persicum (Amrollahi-Sharifabadi et al, 2013).
c) CASE REPORT: A 76-year-old man developed acute respiratory failure, necessitating mechanical ventilation, 2 days after unintentionally ingesting Colchicum autumnale. The patient's condition continued to deteriorate, with the development of multiorgan system failure. He died 3 days post ingestion. An autopsy revealed pulmonary edema and bilateral bronchopneumonia (Brvar et al, 2004a).

a) Mendis (1989) reported dyspnea, along with cardiotoxicity, in a patient who had ingested Gloriosa superba tubers(Mendis, 1989).

a) Tachypnea has been reported two days after the accidental ingestion of Colchicum autumnale (meadow saffron) (Sundov et al, 2005).

a) SUMMARY: Seizures have been reported in children after ingestion of Gloriosa superba (Aleem, 1992) and following overdose in an adult (Gooneratne et al, 2014).
b) CASE REPORT: A 28-year-old woman intentionally ingested Gloriosa superba tubers and 6 hours later she had profuse vomiting, diarrhea and abdominal pain. Upon admission, she was alert and decontaminated with activated charcoal. She was progressing well until day 5 when she developed generalized tonic-clonic seizures and hypocalcemia was also noted (calcium 0.9 mmol/L (1.1 to 1.4). By day 7, her level of consciousness declined with a Glasgow coma scale score of 6/15. Laboratory studies were within normal limits with the exception of mildly elevated liver enzymes. Diagnostic studies, including a CT scan of the head and lumbar puncture, were negative. A serological work-up was also negative. An EEG detected bilateral diffuse slow waves that were suggestive of encephalopathy. In addition, a MR brain scan showed T2 hyper intensities in the caudate and lentiform nuclei of the basal ganglia that are consistent with toxic encephalopathy; the thalamic regions were unaffected. With supportive care, her neurologic function improved (Glasgow coma scale score 11/15) in about 2 weeks and she remained clinically stable (Gooneratne et al, 2014).
c) LACK OF EFFECT: In a series of 6 fatal cases of Gloriosa superba intoxication, there were no neurologic manifestations (Nagaratnam et al, 1973).

a) Ascending paralysis (polyneuropathy) has been reported with Gloriosa superba overdose (Agunawela & Fernando, 1971).

a) General weakness, confusion, agitation, and hallucinations have been reported 2 to 8 days after the accidental ingestion of Colchicum autumnale (meadow saffron/autumn crocus) (Sundov et al, 2005; Gabrscek et al, 2004).

a) Ingestion often causes numbness of the lips, tongue, and throat. An intense thirst and a burning in the mouth and throat may occur (Mendis, 1989).

a) Within 2 to 12 hours, nausea, vomiting, diarrhea, dysphagia, and severe abdominal cramps develop. These symptoms may persist for 10 to 15 days (Premaratna et al, 2015; Boisrame-Helms et al, 2015; Gooneratne et al, 2014; Sannohe et al, 2002; Sundov et al, 2005; Flesch et al, 2002; van Zoelen et al, 2002; Brncic et al, 2001; Danel et al, 2001; Nagaratnam et al, 1973).
b) INCIDENCE: In a series of 49 patients with Gloriosa superba poisoning 2 (4%) developed nausea, 27 (54%) had vomiting, 11 (22%) developed diarrhea and 20 (40%) complained of abdominal pain (Fernando & Fernando, 1990).
c) Abdominal pain, nausea and vomiting, and watery diarrhea have been reported several hours after the accidental ingestion of Colchicum autumnale (meadow saffron/autumn crocus) (Sundov et al, 2005; Brvar et al, 2004; Brvar et al, 2004a; Gabrscek et al, 2004).

a) CASE REPORT: Acute pancreatitis with elevated lipase levels was reported in a 71-year-old woman who unintentionally ingested Colchicum autumnale (autumn crocus). The lipase levels normalized with supportive care (Brvar et al, 2004).
b) CASE REPORT: Elevated plasma lipase and amylase levels [15.1 ukat/L (normal 0 to 2.50 ukat/L) and 4.50 ukat/L (normal 0 to 2.50 ukat/L), respectively] were reported in a 43-year-old woman approximately 6 days after unintentionally ingesting Colchicum autumnale. The pancreatic enzyme levels normalized with supportive care (Gabrscek et al, 2004).

a) Bacterial sepsis may occur later in the course of colchicine plant poisoning (Flesch et al, 2002).

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) 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) 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) 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) CASE REPORT: A 68-year-old woman inadvertently ingested C. autumnale mistaking the plant for wild leeks. Several days after exposure, the patient developed severe shock and multi-organ failure and was admitted to an ICU setting. Laboratory studies showed evidence of numerous clinical events including pancytopenia (requiring blood products), acute liver and renal failure, rhabdomyolysis, severe metabolic acidosis, and cardiac failure. A peak colchicine (10 ng/mL; therapeutic range, 0.6 mg/dL) plasma concentration was reached on day 4. Cardiogenic shock was initially treated with dobutamine (10 mcg/kg/min) and close hemodynamic monitoring including Swan-Ganz and echocardiography. A transthoracic echocardiography revealed global hypokinesia with a left ventricular ejection fraction of 5% to 10%, severe right ventricular dysfunction with moderate tricuspid regurgitation. However, despite these efforts hemodynamic instability persisted and the patient was started on extracorporeal life support (ECLS) at a rate of 3.5 L/min and 3800 rev/min. Gradually, her cardiac function improved and ECLS was removed on day 10. Ongoing clinical complications included sudden arrhythmias with third-degree atrioventricular block on day 12 with cardiac arrest that was treated successfully with resuscitation. Persistent renal failure required intermittent hemodialysis until day 23 and mechanical ventilation was needed until day 20. By day 24, the patient had completely recovered from multi-organ failure and was discharged to home with no permanent sequelae (Boisrame-Helms et al, 2015).

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, 2010; 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) When half a molar dose of Fab fragments compared to the colchicine dose was given intravenously and intraperitoneally, 80 percent of the mice survived, and at one-eighth molar, 20 percent survived (Urtizberea et al, 1990; Scherrmann et al, 1990).
b) This treatment has NOT been tried on humans.

a) Colchicine plasma concentration at 6 hours post-ingestion of 40 flowers of Colchicum autumnale was 3.8 nanograms/milliliter (normal 0.3 to 2.4 nanograms/milliliter). The estimated amount of colchicine in the flowers was 17.1 to 102.7 milligrams. The patient survived following symptomatic therapy (Danel et al, 2001).
b) Serum and urine colchicine levels were 5 mcg/L and 30 mcg/L, respectively, 3 days after a 71-year-old woman unintentionally ingested an unknown amount of Colchicum autumnale (autumn crocus) (Brvar et al, 2004).
c) A serum colchicine level was 14 mcg/L in a 76-year-old man approximately 3 days after unintentionally ingesting 2 whole Colchicum autumnale plants. The total estimated colchicine dose ingested was 10 to 60 mg (0.14 to 0.82 mg/kg). He died 3 days after ingestion (Brvar et al, 2004a).