Contact Us    Contact Us     |     Feedback
MOBILE VIEW  | 

SPIROGERMANIUM

Export To Excel

Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Spirogermanium is a germanium metal containing azaspirane compound with antitumor, antiarthritic, and immunoregulatory activities (DiMartino et al, 1986).

Specific Substances

    1) NSC 192965
    2) 2-aza-8-germaspiro (4,5) decane-2-propanamine,
    3) 8, 8-diethyl-N, N-dimethyl-, dihydrochloride
    4) Spiro-32
    5) Molecular Formula: C17-H36-Ge-N2
    6) SPIROGERMANIUM DIHYDROCHLORIDE

Available Forms Sources

    A) SOURCES
    1) For clinical studies this agent can be obtained through Unimed of The Investigation Drug Branch NCI, Bethesda, MD. It is in 20 mL vials of 10 g of spirogermanium hydrochloride in normal saline and preservatives, pH is adjusted to 5.9 to 6.0 (Slavik et al, 1983). As of 2000, spirogermanium is not manufactured by Unimed, and no further information could be provided on this agent (Personal Communication, 2000).
    B) USES
    1) At the time of this review, Phase I and II trials have been conducted with spirogermanium. Little data has been reported in the literature on spirogermanium. The most recent literature is based on a Phase II trial conducted by Novik et al (1999) in which further investigation of this agent in the treatment of advanced gastric carcinoma was not indicated based on low response rate and relatively high toxicities.

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Phase I clinical studies have not shown cumulative hematological, renal, or hepatic toxicity. Phase II studies have shown significant neurotoxicity which included blurred vision, vertigo, confusion, head tremor, EEG abnormalities, and sensory neuropathy. In 1999, a Phase II trial for the treatment of advanced gastric carcinoma was discontinued, due to a relatively high toxicity profile.
    0.2.4) HEENT
    A) Nystagmus has been seen in animals.
    0.2.5) CARDIOVASCULAR
    A) Phlebitis has been seen following human therapeutic dosing.
    0.2.7) NEUROLOGIC
    A) Seizures have been seen when animals have been given lethal injections. A human patient receiving 550 mg/m(2) IV developed a grand mal seizure.
    B) Tremors, lethargy, dizziness, ataxia, visual distortion, and paresthesias have been seen when this agent has been given intravenously.
    C) Hallucinations have been reported in phase two clinical studies.
    0.2.8) GASTROINTESTINAL
    A) Necrosis of the gastrointestinal mucosa was seen in fatally poisoned animals.
    0.2.9) HEPATIC
    A) Liver function abnormalities were reported in fatally poisoned animals.
    0.2.15) MUSCULOSKELETAL
    A) IM injection in animals has resulted in local necrosis, hemorrhage, edema, and granulation tissue.

Laboratory Monitoring

    A) Monitor liver enzymes for elevated hepatic transaminases.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) There have been few overdose cases reported in the literature. There is no specific antidote. The most prominent serious effect after IV administration is seizures. Other neurologic effects are reversed with either dose reduction, administration rate reduction, or cessation of therapy.
    B) EMESIS: Ipecac-induced emesis is not recommended because of the potential for seizures.
    C) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    D) GASTRIC LAVAGE: Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in the head down left lateral decubitus position or by endotracheal intubation. Control any seizures first.
    1) CONTRAINDICATIONS: Loss of airway protective reflexes or decreased level of consciousness in unintubated patients; following ingestion of corrosives; hydrocarbons (high aspiration potential); patients at risk of hemorrhage or gastrointestinal perforation; and trivial or non-toxic ingestion.
    E) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 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) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 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).
    1) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
    2) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.

Range Of Toxicity

    A) A dose of 800 to 900 mg (550 mg/m(2)) caused grand mal seizures, which was reversed by diazepam.

Clinical Effects

Summary Of Exposure

    A) Phase I clinical studies have not shown cumulative hematological, renal, or hepatic toxicity. Phase II studies have shown significant neurotoxicity which included blurred vision, vertigo, confusion, head tremor, EEG abnormalities, and sensory neuropathy. In 1999, a Phase II trial for the treatment of advanced gastric carcinoma was discontinued, due to a relatively high toxicity profile.

Heent

    3.4.1) SUMMARY
    A) Nystagmus has been seen in animals.
    3.4.3) EYES
    A) NYSTAGMUS was seen in beagles given in excess of 100 mg/m(2) IV (Schein et al, 1980).

Cardiovascular

    3.5.1) SUMMARY
    A) Phlebitis has been seen following human therapeutic dosing.
    3.5.2) CLINICAL EFFECTS
    A) PHLEBITIS
    1) Peripheral phlebitis was seen at most IV dosing levels (Slavik et al, 1983).

Neurologic

    3.7.1) SUMMARY
    A) Seizures have been seen when animals have been given lethal injections. A human patient receiving 550 mg/m(2) IV developed a grand mal seizure.
    B) Tremors, lethargy, dizziness, ataxia, visual distortion, and paresthesias have been seen when this agent has been given intravenously.
    C) Hallucinations have been reported in phase two clinical studies.
    3.7.2) CLINICAL EFFECTS
    A) SEIZURE
    1) CASE REPORT - A patient who received approximately 550 mg/m(2) IV developed a grand mal seizure.
    B) DROWSY
    1) Lethargy lasting up to 12 to 18 hours was noted in humans given 32 mg/m(2) IV over 5 minutes. Dizziness was also seen (Schein et al, 1980).
    C) CENTRAL NERVOUS SYSTEM FINDING
    1) Neurotoxicity which included lethargy, dizziness, ataxia, visual distortion, nystagmus, and paresthesias was seen when spirogermanium was given IV. Increasing the rate of administration and the dose increased the symptoms.
    2) At 160 mg/m(2) there were NO EEG changes despite symptoms in one study (Schein et al, 1980), but EEG changes (unspecified) were reported in 2 of 15 patients in phase II studies by Dexeus et al (1986).
    3) There was no evidence of cumulative toxicity or sequelae (Schein et al, 1980). Moderate to severe, but reversible, neurotoxicity requiring cessation of therapy has been reported in phase II trials (Dexeus et al, 1986).
    D) HALLUCINATIONS
    1) Hallucinations have been reported in phase II studies (Kuebler et al, 1984).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) SEIZURES
    a) Lethal doses given to mice and beagles produced seizures immediately after IV injection (Schein et al, 1980)
    2) TREMOR
    a) BEAGLES - Tremors as well as piloerection and nystagmus are seen in beagles given in excess of 100 mg/m(2) IV (Schein et al, 1980).

Gastrointestinal

    3.8.1) SUMMARY
    A) Necrosis of the gastrointestinal mucosa was seen in fatally poisoned animals.
    3.8.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) INTESTINAL NECROSIS
    a) Necrosis of the gastrointestinal mucosa was seen in animals fatally poisoned with intravenous spirogermanium (Schein et al, 1986).

Hepatic

    3.9.1) SUMMARY
    A) Liver function abnormalities were reported in fatally poisoned animals.
    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HEPATIC FUNCTION ABNORMAL
    a) Liver function abnormalities (type not specified) were reported in beagles fatally poisoned IV (Schein et al, 1986). Dexeus et al (1986) reported reversible elevations of hepatic transaminase 2 to 5 times normal in 4 of 15 patients.

Musculoskeletal

    3.15.1) SUMMARY
    A) IM injection in animals has resulted in local necrosis, hemorrhage, edema, and granulation tissue.
    3.15.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) INJECTION SITE REACTION
    a) Intramuscular injection in animals resulted in local necrosis, hemorrhage, edema, and granulation tissue (Henry et al, 1980).

Immunologic

    3.19.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) NECROSIS ISCHEMIC
    a) DOGS - Focal necrosis of lymphatics was seen in dogs fatally poisoned IV (Schein et al, 1986).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor liver enzymes for elevated hepatic transaminases.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Monitor liver enzymes due to reported elevated hepatic transaminase (Dexeus et al, 1986).

Methods

    A) CHROMATOGRAPHY
    1) Can be determined by gas chromatography (Slavik et al, 1983).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Monitor liver enzymes for elevated hepatic transaminases.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) EMESIS/NOT RECOMMENDED
    1) EMESIS: Ipecac-induced emesis is not recommended because of the potential for seizures.
    B) ACTIVATED CHARCOAL -
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    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).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    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).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) EMESIS/NOT RECOMMENDED
    1) EMESIS: Ipecac-induced emesis is not recommended because of the potential for seizures.
    B) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    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.
    2) CHARCOAL DOSE
    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).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    C) GASTRIC LAVAGE
    1) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).
    a) Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.
    2) PRECAUTIONS:
    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.
    3) LAVAGE FLUID:
    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.
    4) COMPLICATIONS:
    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).
    5) CONTRAINDICATIONS:
    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.
    6.5.3) TREATMENT
    A) SEIZURE
    1) SUMMARY
    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).
    2) DIAZEPAM
    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 .
    3) NO INTRAVENOUS ACCESS
    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).
    4) LORAZEPAM
    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).
    5) PHENOBARBITAL
    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).
    6) OTHER AGENTS
    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):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).

Abstracts

Case Reports

    A) ADULT
    1) One 69-year-old patient given an infusion of 800 mg/m(2) for 20 minutes developed a 3-minute long tonic-clonic grand mal seizure. The actual amount received was 800 to 900 mg (or 550 mg/m(2)). The seizure was terminated 3 minutes later with 4 mg of diazepam IV (Schein et al, 1980).

Range Of Toxicity

Summary

    A) A dose of 800 to 900 mg (550 mg/m(2)) caused grand mal seizures, which was reversed by diazepam.

Therapeutic Dose

    7.2.1) ADULT
    A) ROUTE OF ADMINISTRATION
    1) INTRAVENOUS - 50 to 120 milligrams/square meter over 30 minutes, given 2 to 3 times weekly (Schein et al, 1980) Slavik et al, 1983).

Maximum Tolerated Exposure

    A) ACUTE
    1) A dose of 800 to 900 milligrams (550 milligrams/square meter) caused a grand mal seizure which was reversed by diazepam (Schein et al, 1980).

Toxicity Information

    7.7.1) TOXICITY VALUES

Pharmacology Toxicology

Pharmacologic Mechanism

    A) As an antitumor agent it is thought to inhibit DNA, RNA and protein synthesis (Schein et al, 1980).

Physicochemical

Physical Characteristics

    A) SPIROGERMANIUM: oil
    B) SPIROGERMANIUM DIHYDROCHLORIDE: crystals

Molecular Weight

    A) SPIROGERMANIUM DIHYDROCHLORIDE: 414

References

General Bibliography

    1) AMA Department of DrugsAMA Department of Drugs: AMA Evaluations Subscription, American Medical Association, Chicago, IL, 1992.
    2) Alaspaa AO, Kuisma MJ, Hoppu K, et al: Out-of-hospital administration of activated charcoal by emergency medical services. Ann Emerg Med 2005; 45:207-12.
    3) Benfenati E, Zucchetti M, & D'Incalci M: Identification of microsomal metabolites of spirogermanium. Anticancer Res 1989; 9:507-510.
    4) Brophy GM, Bell R, Claassen J, et al: Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012; 17(1):3-23.
    5) Caravati EM, Knight HH, & Linscott MS: Esophageal laceration and charcoal mediastinum complicating gastric lavage. J Emerg Med 2001; 20:273-276.
    6) Chamberlain JM, Altieri MA, & Futterman C: A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children. Ped Emerg Care 1997; 13:92-94.
    7) Chin RF , Neville BG , Peckham C , et al: Treatment of community-onset, childhood convulsive status epilepticus: a prospective, population-based study. Lancet Neurol 2008; 7(8):696-703.
    8) Choonara IA & Rane A: Therapeutic drug monitoring of anticonvulsants state of the art. Clin Pharmacokinet 1990; 18:318-328.
    9) Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.
    10) Dagnone D, Matsui D, & Rieder MJ: Assessment of the palatability of vehicles for activated charcoal in pediatric volunteers. Pediatr Emerg Care 2002; 18:19-21.
    11) Dexeus FH, Logothetis C, & Samuels ML: Phase II study of spirogermanium in metastatic prostate cancer. Cancer Treat Reports 1986; 70:1129-1130.
    12) DiMartino MJ, Lee JC, & Badger AM: Antiarthritic and immunoregulatory activity of spirogermanium. J Pharmacol Exp Ther 1986; 236:103-236.
    13) Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.
    14) FDA: Poison treatment drug product for over-the-counter human use; tentative final monograph. FDA: Fed Register 1985; 50:2244-2262.
    15) Golej J, Boigner H, Burda G, et al: Severe respiratory failure following charcoal application in a toddler. Resuscitation 2001; 49:315-318.
    16) Graff GR, Stark J, & Berkenbosch JW: Chronic lung disease after activated charcoal aspiration. Pediatrics 2002; 109:959-961.
    17) Guenther Skokan E, Junkins EP, & Corneli HM: Taste test: children rate flavoring agents used with activated charcoal. Arch Pediatr Adolesc Med 2001; 155:683-686.
    18) Harris CR & Filandrinos D: Accidental administration of activated charcoal into the lung: aspiration by proxy. Ann Emerg Med 1993; 22:1470-1473.
    19) Hegenbarth MA & American Academy of Pediatrics Committee on Drugs: Preparing for pediatric emergencies: drugs to consider. Pediatrics 2008; 121(2):433-443.
    20) Henry MC, Rosen E, & Port CD: Toxicity of spirogermanium in mice and dogs after IV or IM administration. Cancer Treat Reports 1980; 64:1207-1210.
    21) Hvidberg EF & Dam M: Clinical pharmacokinetics of anticonvulsants. Clin Pharmacokinet 1976; 1:161.
    22) Kuebler JP, Tormey DC, & Harper GR: Phase II study of spirogermanium in advanced breast cancer. Cancer Treat Reports 1984; 68:1515-1516.
    23) Loddenkemper T & Goodkin HP: Treatment of Pediatric Status Epilepticus. Curr Treat Options Neurol 2011; Epub:Epub.
    24) Manno EM: New management strategies in the treatment of status epilepticus. Mayo Clin Proc 2003; 78(4):508-518.
    25) None Listed: Position paper: cathartics. J Toxicol Clin Toxicol 2004; 42(3):243-253.
    26) Personal Communication: Personal Communication: Unimed Customer Service Representative, Phone number 1-800-541-3492. Unimed Customer Service, 2000.
    27) Pollack MM, Dunbar BS, & Holbrook PR: Aspiration of activated charcoal and gastric contents. Ann Emerg Med 1981; 10:528-529.
    28) Product Information: diazepam IM, IV injection, diazepam IM, IV injection. Hospira, Inc (per Manufacturer), Lake Forest, IL, 2008.
    29) Product Information: lorazepam IM, IV injection, lorazepam IM, IV injection. Akorn, Inc, Lake Forest, IL, 2008.
    30) Rau NR, Nagaraj MV, Prakash PS, et al: Fatal pulmonary aspiration of oral activated charcoal. Br Med J 1988; 297:918-919.
    31) Schein PS, Slavik M, & Smythe T: Phase I clinical trial of spirogermanium. Cancer Treat Reports 1980; 64:1051-1056.
    32) Scott R, Besag FMC, & Neville BGR: Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomized trial. Lancet 1999; 353:623-626.
    33) Spiller HA & Rogers GC: Evaluation of administration of activated charcoal in the home. Pediatrics 2002; 108:E100.
    34) Sreenath TG, Gupta P, Sharma KK, et al: Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children: A randomized controlled trial. Eur J Paediatr Neurol 2009; Epub:Epub.
    35) Thakore S & Murphy N: The potential role of prehospital administration of activated charcoal. Emerg Med J 2002; 19:63-65.
    36) Vale JA, Kulig K, American Academy of Clinical Toxicology, et al: Position paper: Gastric lavage. J Toxicol Clin Toxicol 2004; 42:933-943.
    37) Vale JA: Position Statement: gastric lavage. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. J Toxicol Clin Toxicol 1997; 35:711-719.