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HEXAPROPYMATE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Hexapropymate is a carbamate compound which is used as a sedative-hypnotic in the treatment of insomnia. It has properties similar to those of ethinamate and the barbiturates (Gustafsson et al, 1989).

Specific Substances

    1) L-2103
    2) Propinylcyclohexanol carbamate
    3) 1-(prop-2-ynyl)cyclohexyl carbamate
    4) CAS 358-52-1
    5) 1-(2-propynyl)cyclohexanol carbamate
    6) 1-carbamoyloxy-1-(2-propynyl)cyclohexane
    7) hexopropynate
    8) Molecular Formula: C10-H15-N-O2

Available Forms Sources

    A) SOURCES
    1) Hexapropymate is not available in the United States. Brand names in other countries are: Biradon(R) (Argentina), Merinax(R) (Belgium, France, Italy, Netherlands, Spain, Switzerland), and Modirax(R) (Sweden) (JEF Reynolds , 1989).
    2) This agent was withdrawn from the market in Sweden in April of 1989 (Gustafsson et al, 1989).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) OVERDOSE - hypotension, hypothermia, respiratory depression, and coma may develop. The clinical picture is similar to that seen with barbiturates.
    B) A number of the fatalities seen with this drug have also been complicated by severe addiction problems.
    0.2.5) CARDIOVASCULAR
    A) Hypotension has been seen in several overdose cases. Tachycardia has been reported, but has been complicated by hypothermia and hypoxia.
    0.2.6) RESPIRATORY
    A) Respiratory depression may lead to hypoxia and cyanosis. Prolonged respiratory support may be required.
    0.2.7) NEUROLOGIC
    A) Coma is a common complication, and may last for several days.
    0.2.14) DERMATOLOGIC
    A) Rashes have been reported and in one case, a sensitivity reaction, resulting in thrombopenic purpura was seen.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    B) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, no data were available to assess the carcinogenic or mutagenic potential of this agent.

Laboratory Monitoring

    A) No specific laboratory measures are needed unless otherwise clinically indicated. Monitor vital signs. If respiratory depression is present, monitor pulse oximetry and/or arterial blood gases. Hexapropymate levels do not appear to correlate well with depth of coma.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Because CNS depression may be seen in as little as 15 to 30 minutes, emesis is not recommended.
    B) 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.
    C) 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.
    D) Support respiratory and cardiovascular function; be prepared to manage airway and provide ventilatory support.
    E) HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine (5 to 20 mcg/kg/min) or norepinephrine (ADULT: begin infusion at 0.5 to 1 mcg/min; CHILD: begin infusion at 0.1 mcg/kg/min); titrate to desired response.

Range Of Toxicity

    A) Sixteen to 40 grams have been survived with adequate respiratory and cardiovascular support.

Clinical Effects

Summary Of Exposure

    A) OVERDOSE - hypotension, hypothermia, respiratory depression, and coma may develop. The clinical picture is similar to that seen with barbiturates.
    B) A number of the fatalities seen with this drug have also been complicated by severe addiction problems.

Vital Signs

    3.3.2) RESPIRATIONS
    A) RESPIRATORY DEPRESSION may develop.
    3.3.3) TEMPERATURE
    A) HYPOTHERMIA - Temperatures of 29.9 to 35.2 degrees Centigrade were noted in several severe poisonings reported by Gustafsson et al (1989). The patient reported by Robbins and Brown (1978) was also hypothermic (rectal temperature of 28 degrees Centigrade).
    3.3.4) BLOOD PRESSURE
    A) Severe cases of overdose may present with hypotension.

Cardiovascular

    3.5.1) SUMMARY
    A) Hypotension has been seen in several overdose cases. Tachycardia has been reported, but has been complicated by hypothermia and hypoxia.
    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) Hypotension was seen in several overdose cases (Hassoun et al, 1978; Robbins & Brown, 1978; Noirfalise, 1971; Bonnichsen & Holmgren, 1974) Gustafsson et al, 1989).
    B) CONDUCTION DISORDER OF THE HEART
    1) CASE REPORT - The patient seen by Robbins & Brown (1978) was hypothermic and cyanotic and also had bouts of tachycardia, with evidence of intraventricular block.
    a) An electrocardiogram later showed sinus rhythm, apparent short PR intervals, delta waves, and rSR pattern suggestive of a type B Wolff-Parkinson-White syndrome. It is unclear if these cardiac effects were due to hypothermia, hypoxia, or hexapropymate.

Respiratory

    3.6.1) SUMMARY
    A) Respiratory depression may lead to hypoxia and cyanosis. Prolonged respiratory support may be required.
    3.6.2) CLINICAL EFFECTS
    A) APNEA
    1) Assisted ventilation was required in 7 of 8 cases seen in one study; in one case respiratory support was necessary for 4 days. The range of duration of assisted ventilation was 12 to 84 hours (Gustafsson et al, 1989).

Neurologic

    3.7.1) SUMMARY
    A) Coma is a common complication, and may last for several days.
    3.7.2) CLINICAL EFFECTS
    A) COMA
    1) Coma was a reported effect of hexapropymate overdose (Hassoun et al, 1978; Noirfalise, 1971; Robbins & Brown, 1978; Gary & Tresnewsky, 1983). In a study by Gustaffsson et al (1989), there did not appear to be any relationship between the depth or duration of coma and the serum concentration of hexapropymate. The duration of coma in this case series ranged from 18 to 96 hours.

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) LIVER DAMAGE
    1) One case report mentions mild hepatocellular damage which gradually resolved (Robbins & Brown, 1978).

Dermatologic

    3.14.1) SUMMARY
    A) Rashes have been reported and in one case, a sensitivity reaction, resulting in thrombopenic purpura was seen.
    3.14.2) CLINICAL EFFECTS
    A) THROMBOCYTOPENIC PURPURA
    1) Thrombocytopenic purpura has been seen as a sensitivity reaction to hexapropymate (Siguier et al, 1971).
    B) ERUPTION
    1) CASE REPORT - One overdose patient had erythematous and urticarial macules appear on his legs in the first few days following a hexapropymate overdose.
    a) It was not determined if these were due to the hexapropymate or to the ampicillin which was administered during his hospital stay (Robbins & Brown, 1978).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) THROMBOCYTOPENIC PURPURA
    1) Thrombocytopenic purpura has been seen as a sensitivity reaction to hexapropymate (Siguier et al, 1971).

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    B) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    3.20.2) TERATOGENICITY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) At the time of this review, no data were available to assess the carcinogenic or mutagenic potential of this agent.
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the carcinogenic or mutagenic potential of this agent.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No specific laboratory measures are needed unless otherwise clinically indicated. Monitor vital signs. If respiratory depression is present, monitor pulse oximetry and/or arterial blood gases. Hexapropymate levels do not appear to correlate well with depth of coma.

Methods

    A) CHROMATOGRAPHY
    1) A gas chromatographic method of determining hexapropymate in serum is described by Gustafsson et al (1989). The limit of detection with this method was 2.7 mg/L (15 micromoles/liter), with a coefficient of variation of 5%.
    2) Another method using extraction and then thin layer and/or gas chromatography is cited in a paper by Hassoun et al (1978).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) No specific laboratory measures are needed unless otherwise clinically indicated. Monitor vital signs. If respiratory depression is present, monitor pulse oximetry and/or arterial blood gases. Hexapropymate levels do not appear to correlate well with depth of coma.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) EMESIS/NOT RECOMMENDED -
    1) Emesis is NOT recommended because CNS depression may be seen within 15 to 30 minutes.
    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 is NOT recommended because the onset of CNS depression may be as soon as 15 to 30 minutes.
    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) SUPPORT
    1) There is no specific antidote. Treatment is directed at maintaining respiratory and cardiovascular support. Respiratory support may be required for days. Patients should be observed for signs of aspiration. Monitor vital signs. Monitor pulse oximetry and/or arterial blood gases in patients with coma or respiratory depression.
    2) Consider arterial blood gases in patients with inadequate respiratory support.
    B) HYPOTENSIVE EPISODE
    1) SUMMARY
    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.
    2) DOPAMINE
    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).
    3) NOREPINEPHRINE
    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
    1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
    2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).

Enhanced Elimination

    A) SUMMARY
    1) This drug has a relatively large estimated volume of distribution (1.5 to 3.5 liters per kilogram) so hemodialysis and hemoperfusion are not expected to be useful (Gustafsson et al, 1989).

Abstracts

Case Reports

    A) ACUTE EFFECTS
    1) ADULT
    a) A 41-year-old woman ingested 40 grams and was admitted in coma responsive only to severe pain stimuli. Gastric lavage was attempted and failed due to technical problems. At 24 hours postingestion, she was still unconscious, but did not require ventilatory assistance.
    1) Two days postingestion she developed tachycardia, tachypnea and cyanosis, probably due to aspiration. She was intubated and given assisted ventilation for 3 hours. The remainder of the clinical course was uneventful.
    2) Her maximum blood concentration was 16.5 mcg/L (90 micromoles/liter), recorded at 28 hours postingestion (Gustafsson et al, 1989).
    b) A 40-year-old man was admitted to the intensive care ward after ingesting an estimated 20 grams of hexapropymate over 36 hours (Gustafsson et al, 1989). The patient was deeply comatose, and did not react to painful stimuli. His breathing was irregular, and blood pressure was 75/50 mmHg.
    1) He was lavaged, intubated and mechanically ventilated for 18 hours. Body temperature on admission was 34.7 degrees Centigrade but normalized within 10 hours. He was unconscious for 37 hours, but recovered with no other complications.
    2) His initial serum level was 33 mcg/L (180 micromoles/liter) with an estimated terminal half-life of 21 hours.

Range Of Toxicity

Summary

    A) Sixteen to 40 grams have been survived with adequate respiratory and cardiovascular support.

Therapeutic Dose

    7.2.1) ADULT
    A) GENERAL
    1) The normal dose is 400 milligrams taken at bedtime (JEF Reynolds , 1989).

Maximum Tolerated Exposure

    A) CASE REPORTS
    1) The patient reported by Robbins and Brook (1978) ingested 16 grams and with supportive care recovered without sequelae. Gustafsson et al (1989) reported a case of ingestion of 20 grams and one of 40 grams that also recovered with supportive care.

Physicochemical

Physical Characteristics

    A) Seen as crystals after isolation from petroleum ether or dioxane (Windholz, 1983)

Molecular Weight

    A) 181.2

References

General Bibliography

    1) 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.
    2) Bonnichsen R & Holmgren P: A report on autopsy cases involving hexapropymate. Archivio di Medicina Legale, Sociale e Criminologia 1974; 10:1-8.
    3) Caravati EM, Knight HH, & Linscott MS: Esophageal laceration and charcoal mediastinum complicating gastric lavage. J Emerg Med 2001; 20:273-276.
    4) Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.
    5) 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.
    6) Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.
    7) FDA: Poison treatment drug product for over-the-counter human use; tentative final monograph. FDA: Fed Register 1985; 50:2244-2262.
    8) Gary NE & Tresnewsky O: Clinical aspects of drug intoxication: barbiturates and a potpourri of other sedatives, hypnotics, and tranquilizers. Heart and Lung 1983; 12:122-127.
    9) Golej J, Boigner H, Burda G, et al: Severe respiratory failure following charcoal application in a toddler. Resuscitation 2001; 49:315-318.
    10) Graff GR, Stark J, & Berkenbosch JW: Chronic lung disease after activated charcoal aspiration. Pediatrics 2002; 109:959-961.
    11) 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.
    12) Gustafsson LL, Berg A, & Magnusson A: Hexapropymate self-poisoning causes severe and long-lasting clinical symptoms. Med Toxicol Adverse Drug Exp 1989; 4:295-301.
    13) Harris CR & Filandrinos D: Accidental administration of activated charcoal into the lung: aspiration by proxy. Ann Emerg Med 1993; 22:1470-1473.
    14) Hassoun A, von Birst P, & Vandendriessche M: Une methode simple et raphide pour la recherche et le dosage de l'hexapropymate dans les milieux biologiques et les organes. Toxicol Eur Research 1978; 1:185-188.
    15) JEF Reynolds : Martindale: The Extra Pharmacopoeia (CD-ROM Version). The Pharmaceutical Press. London, UK (Internet Version). Edition expires 1989; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    16) Kleinman ME, Chameides L, Schexnayder SM, et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Part 14: pediatric advanced life support. Circulation 2010; 122(18 Suppl.3):S876-S908.
    17) Leyssens L, van Boven M, & Daenens P: Biotransformation of hexapropymate in man. Part 2: isolation and identification of metabolites. Pharmazie 1984; 39:114-117.
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    19) None Listed: Position paper: cathartics. J Toxicol Clin Toxicol 2004; 42(3):243-253.
    20) Peberdy MA , Callaway CW , Neumar RW , et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care science. Part 9: post–cardiac arrest care. Circulation 2010; 122(18 Suppl 3):S768-S786.
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    22) Product Information: dopamine hcl, 5% dextrose IV injection, dopamine hcl, 5% dextrose IV injection. Hospira,Inc, Lake Forest, IL, 2004.
    23) Product Information: norepinephrine bitartrate injection, norepinephrine bitartrate injection. Sicor Pharmaceuticals,Inc, Irvine, CA, 2005.
    24) Rau NR, Nagaraj MV, Prakash PS, et al: Fatal pulmonary aspiration of oral activated charcoal. Br Med J 1988; 297:918-919.
    25) Robbins G & Brown AK: Hexapropymate self-poisoning. Br Med J 1978; 1:1593.
    26) Siguier F, Godeau P, & Vergoz D: Purpura thrombopenique immuno-allergique par senibilisation a l'hexapropymate. Ann Med Interne (Paris) 1971; 122:435-438.
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    28) Thakore S & Murphy N: The potential role of prehospital administration of activated charcoal. Emerg Med J 2002; 19:63-65.
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