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CHLORALOSE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Alpha chloralose is a rodenticide used in the control of bird pests and to kill mice, rats, and moles. Alpha chloralose is also used as an anesthetic for veterinary surgery. The toxicity profile of this agent resembles that of chloral hydrate and strychnine. Chloralose possesses central depressant effects producing sedation and anesthesia as well as a stimulant action, resulting in seizures.

Specific Substances

    1) ( R )-1,2-O-(2,2,2-Trichloroethylidene)-alpha-D-
    2) glucofuranose
    3) 1,2-O-(2,2,2-Trichloroethylidene)-alpha-D-
    4) glucofuranose
    5) 2-Chloralose
    6) AGC
    7) Alfamat
    8) Alpha-chloralose
    9) Alpha-D-Glucochloralose
    10) Alpha-D-Glucofuranose, 1,2-O-(2,2,2-trichloro
    11) ethylidene)-,(R)-(9Cl)
    12) Alphachloralose
    13) Alphakil
    14) Anhydroglucochloral
    15) Aphosal
    16) Chloralosane
    17) Chloralose
    18) Chloralose DCF
    19) Chloralosane
    20) Dulcidor
    21) Glucochloral
    22) Glucochloralose
    23) Kalmettumsomniferum
    24) Krakalos
    25) Murex
    26) Perglucorat
    27) Somio
    28) Molecular formula: C8-H11-Cl3-O6
    29) CAS 15879-93-3
    30) (R)-1,2-O-(2,2,2-TRICHLOROETHYLIDENE)-ALPHA-D-GLUCOFURANOSE
    31) 1,2-O-(2,2,2-TRICHLOROETHYLIDENE)-ALPHA-D-GLUCOFURANOSE
    32) ALPHA-D-GLUCOFURANOSE, 1,2-O-(2,2,2-TRICHLOROETHYLIDENE) - , (R) - (9CI)
    33) ALPHAKIL (TRADE NAME OF ALPHA CHLORALOSE)
    34) DOLSOM (TRADE NAME)
    35) DORCALM (TRADE NAME)

Available Forms Sources

    A) FORMS
    1) Chloralose is an odorless, white, crystalline solid (Budavari, 1996; MSDS (Material Safety Data Sheet), 1997).
    B) SOURCES
    1) Chloralose is prepared from a chemical condensing of glucose and trichloroacetaldehyde (anhydrous chloral) in the presence of sulfuric acid (Budavari, 1996; Lees, 1972).
    C) USES
    1) Alpha chloralose is most commonly used for the control of bird pests and as a rodenticide to kill mice, rats and moles (Thomas et al, 1988).
    2) In experimental laboratory animals, chloralose has been used as an anesthetic since it has little effect on the autonomic nervous system. This agent was formerly used for its hypnotic properties, particularly in France (Thomas et al, 1988; JEF Reynolds , 1999).
    3) In humans, chloralose at one time was used as an activating agent in electroencephalography to assist in diagnosis of seizure disorders and other brain lesions (Lees, 1972; Balis & Monroe, 1964).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) WITH POISONING/EXPOSURE
    1) Acute toxic chloralose ingestions have been reported to result in sedation, coma, respiratory depression, myoclonic or generalized seizures, miosis, hypersalivation, increased tracheal secretions, and hypotension. This agent paradoxically possesses both central depressant effects producing sedation and anesthesia as well as a stimulant action. Coma is usually accompanied by excitability, but in severe overdoses there may be flaccidity.
    2) Prognosis is generally favorable if symptomatic care is provided early. Recovery generally occurs within 48 hours following symptomatic care, although suicidal fatalities have been reported. Pulmonary infection (likely from aspiration) may occur as the patient recovers from the symptoms of the acute overdose.
    0.2.3) VITAL SIGNS
    A) WITH POISONING/EXPOSURE
    1) Hypothermia and hyperthermia have been reported.
    0.2.5) CARDIOVASCULAR
    A) WITH POISONING/EXPOSURE
    1) Tachycardia is a common finding. Hypotension may occur.
    0.2.6) RESPIRATORY
    A) WITH POISONING/EXPOSURE
    1) Respiratory depression, requiring artificial ventilation, and pulmonary edema may commonly occur following large overdoses.
    0.2.7) NEUROLOGIC
    A) WITH POISONING/EXPOSURE
    1) Headache and sudden drowsiness rapidly followed by coma and myoclonus or generalized seizure is commonly reported following chloralose ingestions. Seizures are often refractory to treatment with the usual anticonvulsants and should be treated with benzodiazepines.
    2) Massive poisonings result in hyperreflexia followed by flaccid paralysis and respiratory depression.
    0.2.8) GASTROINTESTINAL
    A) WITH POISONING/EXPOSURE
    1) Increased salivation is a common toxic finding.
    0.2.11) ACID-BASE
    A) WITH POISONING/EXPOSURE
    1) Metabolic acidosis may occur.
    0.2.14) DERMATOLOGIC
    A) WITH POISONING/EXPOSURE
    1) Cyanosis and facial flushing have been reported.
    0.2.20) REPRODUCTIVE
    A) In proestrous rats, chloralose may cause an increased sensitivity of the pituitary to gonadotropin releasing hormone. Other studies on potential reproductive effects of this agent are lacking.

Laboratory Monitoring

    A) Monitor vital signs and pulse oximetry in all symptomatic patients.
    B) Monitor for signs of CNS and respiratory depression.
    C) Monitor EEG for seizure activity.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Treatment is SYMPTOMATIC and SUPPORTIVE.
    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) Endotracheal intubation and mechanical ventilation may be necessary in cases of airway compromise.
    D) 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.
    E) REFRACTORY SEIZURES: Consider continuous infusion of midazolam, propofol, and/or pentobarbital. Hyperthermia, lactic acidosis and muscle destruction may necessitate use of neuromuscular blocking agents with continuous EEG monitoring.
    F) 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.
    G) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
    H) RHABDOMYOLYSIS: Administer sufficient 0.9% saline (10 to 15 mL/kg/hour) to maintain urine output of at least 1 to 2 mL/kg/hour (or greater than 150 to 300 mL/hr). Monitor input and output, serum electrolytes, CK, and renal function. Diuretics may be necessary to maintain urine output, but should only be considered if urine output is inadequate after volume status is restored. Urinary alkalinization is NOT routinely recommended.
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

    A) The oral toxic dose in humans is reported to be 1 to 4 grams. A toxic dose in infants is reported to be 20 mg/kg.
    B) Severe toxicity (coma, seizures, myoclonus, hypothermia, hyperthermia, respiratory failure, metabolic acidosis, rhabdomyolysis) with ultimate survival with aggressive supportive care has been reported after ingestions of up to 30 grams by adults.

Clinical Effects

Summary Of Exposure

    A) WITH POISONING/EXPOSURE
    1) Acute toxic chloralose ingestions have been reported to result in sedation, coma, respiratory depression, myoclonic or generalized seizures, miosis, hypersalivation, increased tracheal secretions, and hypotension. This agent paradoxically possesses both central depressant effects producing sedation and anesthesia as well as a stimulant action. Coma is usually accompanied by excitability, but in severe overdoses there may be flaccidity.
    2) Prognosis is generally favorable if symptomatic care is provided early. Recovery generally occurs within 48 hours following symptomatic care, although suicidal fatalities have been reported. Pulmonary infection (likely from aspiration) may occur as the patient recovers from the symptoms of the acute overdose.

Vital Signs

    3.3.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Hypothermia and hyperthermia have been reported.
    3.3.3) TEMPERATURE
    A) WITH POISONING/EXPOSURE
    1) Hypothermia has been observed following human chloralose ingestions (Rambourg-Schepens et al, 1999), but appears to be more prominent in animals (Thomas et al, 1988).
    2) INCIDENCE - In a case series of 49 patients, hypothermia was reported in 25% of patients and hyperthermia was reported in 44% (Flesch et al, 2000).
    3.3.5) PULSE
    A) WITH POISONING/EXPOSURE
    1) Elevated pulse rates have been reported (Shita et al, 1981).

Heent

    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) Bilateral mydriasis, reacting to light, has been reported following rodenticide ingestions (Rambourg-Schepens et al, 1999; Thomas et al, 1988).
    2) Small pupils, reacting to light, and absent corneal reflexes following a toxic ingestion of chloralose have been reported (Thomas et al, 1988).
    3) Direct ocular exposure to chloralose powder may cause eye irritation (MSDS (Material Safety Data Sheet), 1997).

Cardiovascular

    3.5.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Tachycardia is a common finding. Hypotension may occur.
    3.5.2) CLINICAL EFFECTS
    A) TACHYARRHYTHMIA
    1) WITH POISONING/EXPOSURE
    a) Tachycardia is a common finding following chloralose overdose (Shita et al, 1981; Moene et al, 1968).
    B) HYPOTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) Hypotension may occur following chloralose overdose (Thomas et al, 1988).
    C) HYPOTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) Cardiovascular collapse is an uncommon finding following chloralose overdoses (Shita et al, 1981; Moene et al, 1968).

Respiratory

    3.6.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Respiratory depression, requiring artificial ventilation, and pulmonary edema may commonly occur following large overdoses.
    3.6.2) CLINICAL EFFECTS
    A) ACUTE RESPIRATORY INSUFFICIENCY
    1) WITH POISONING/EXPOSURE
    a) Respiratory depression, requiring artificial ventilation, may occur due to central depressant effects of chloralose (Rambourg-Schepens et al, 1999; Quinio et al, 1995; Thomas et al, 1988); (Manzo et al, 1979).
    b) INCIDENCE - Respiratory failure is a common toxic effect, occurring in 77% of patients in a case series of 49 toxic exposures (Flesch et al, 2000).
    B) ACUTE LUNG INJURY
    1) WITH POISONING/EXPOSURE
    a) Pulmonary edema may commonly occur following chloralose poisoning (Shita et al, 1981).
    C) EXCESSIVE BRONCHIAL SECRETION
    1) WITH POISONING/EXPOSURE
    a) Bronchial hypersecretion appears to be common following overdoses (Shita et al, 1981; Rambourg-Schepens et al, 1999; Moene et al, 1968) and may require atropine to treat the tracheobronchial hypersecretory state (Savin et al, 2003).
    b) INCIDENCE - In a case series of 49 patients, 32% of patients experienced bronchial hypersecretion (Flesch et al, 2000).

Neurologic

    3.7.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Headache and sudden drowsiness rapidly followed by coma and myoclonus or generalized seizure is commonly reported following chloralose ingestions. Seizures are often refractory to treatment with the usual anticonvulsants and should be treated with benzodiazepines.
    2) Massive poisonings result in hyperreflexia followed by flaccid paralysis and respiratory depression.
    3.7.2) CLINICAL EFFECTS
    A) SEIZURE
    1) WITH POISONING/EXPOSURE
    a) Seizures are common following chloralose poisonings. Mild tactile stimulation may trigger the seizures, which are usually myoclonic or generalized, and often refractory to anticonvulsant therapy (Savin et al, 2003; Rambourg-Schepens et al, 1999; Shita et al, 1981; Quinio et al, 1995; Thomas et al, 1988); (Balis & Monroe, 1964; Cornette & Franck, 1970; Moene et al, 1968). Myoclonic reactions may be absent in a small number of poisonings (Shita et al, 1981).
    b) INCIDENCE - In a retrospective series of 49 cases of chloralose poisoning, myoclonus developed in 92 percent and seizures in 14 percent (Flesch et al, 2000).
    B) HYPERREFLEXIA
    1) Neurologic examination is usually non-focal, with active, symmetric tendon reflexes (Shita et al, 1981; Thomas et al, 1988); (Moene et al, 1968).
    C) HEADACHE
    1) WITH POISONING/EXPOSURE
    a) Headache is commonly reported as an initial symptom following poisonings (Rambourg-Schepens et al, 1999).
    D) COMA
    1) WITH POISONING/EXPOSURE
    a) Sudden drowsiness rapidly followed by deep coma and myoclonus is a common finding in chloralose toxicity (Shita et al, 1981; Rambourg-Schepens et al, 1999; Quinio et al, 1995; Manzo et al, 1979; Balis & Monroe, 1964; Cornette & Franck, 1970) and appears to be dose-related (Moene et al, 1968).
    b) INCIDENCE - In a retrospective series of 49 cases of chloralose poisoning, coma developed in 94 percent (Flesch et al, 2000).
    c) DURATION - Coma may last from several hours to several days. In more severe cases, coma is accompanied by flaccidity and respiratory depression (Savin et al, 2003; Thomas et al, 1988).
    E) ELECTROENCEPHALOGRAM ABNORMAL
    1) Slowing of delta waves as seen on EEG appears to be common following chloralose poisoning (Shita et al, 1981; Rambourg-Schepens et al, 1999; Manzo et al, 1979; Cornette & Franck, 1970; Moene et al, 1968). When performed during a seizure, EEG showed abnormal diffuse discharge with no evidence of focal abnormalities. During the interseizure period the EEG pattern was normal (Rambourg-Schepens et al, 1999). Flesch et al (2000) reported 34 cases where EEG showed either an irritative aspect or a more typical aspect of myoclonic and/or epileptic status (Flesch et al, 2000).
    F) FLACCID PARALYSIS
    1) WITH POISONING/EXPOSURE
    a) At very high doses, chloralose produces hyperreflexia and hypersensitivity, which is followed by flaccid paralysis and respiratory depression which may require mechanical ventilation (Thomas et al, 1988).

Gastrointestinal

    3.8.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Increased salivation is a common toxic finding.
    3.8.2) CLINICAL EFFECTS
    A) EXCESSIVE SALIVATION
    1) WITH POISONING/EXPOSURE
    a) Increased salivation is notable within an hour following toxic ingestions and may cause airways obstruction (Thomas et al, 1988); (Shita et al, 1981; Rambourg-Schepens et al, 1999).

Acid-Base

    3.11.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Metabolic acidosis may occur.
    3.11.2) CLINICAL EFFECTS
    A) ACIDOSIS
    1) WITH POISONING/EXPOSURE
    a) Flesch et al (2000) reported metabolic acidosis occurring in 10 out of 41 chloralose poisonings, likely secondary to seizure activity (Flesch et al, 2000).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) LEUKOCYTOSIS
    1) WITH POISONING/EXPOSURE
    a) Leukocytosis was reported in 46% of patients in a case series (n=49) following a toxic exposure to chloralose (Flesch et al, 2000).

Dermatologic

    3.14.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Cyanosis and facial flushing have been reported.
    3.14.2) CLINICAL EFFECTS
    A) FLUSHING
    1) WITH POISONING/EXPOSURE
    a) Facial flushing has been reported following a chloralose ingestion (Rambourg-Schepens et al, 1999). Cyanosis is a common finding following overdoses (Shita et al, 1981).
    B) SKIN IRRITATION
    1) WITH POISONING/EXPOSURE
    a) Prolonged and/or repeated dermal contact may result in skin irritation or dermatitis (MSDS (Material Safety Data Sheet), 1997).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) RHABDOMYOLYSIS
    1) WITH POISONING/EXPOSURE
    a) Rhabdomyolysis is a potential clinical effect following sustained grand mal seizures due to chloralose poisoning (Savin et al, 2003)
    b) INCIDENCE - Flesch et al (2000) reported the occurrence of rhabdomyolysis in 10 out of 21 cases of chloralose poisonings (Flesch et al, 2000).

Reproductive

    3.20.1) SUMMARY
    A) In proestrous rats, chloralose may cause an increased sensitivity of the pituitary to gonadotropin releasing hormone. Other studies on potential reproductive effects of this agent are lacking.
    3.20.3) EFFECTS IN PREGNANCY
    A) ANIMAL STUDIES
    1) In proestrous rats, chloralose may cause an increased sensitivity of the pituitary to gonadotropin releasing hormone (Scialli, 1999). Other studies on potential reproductive effects of this agent are lacking.
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) LACK OF INFORMATION
    1) Studies on lactation effects of chloralose are not yet available.

Carcinogenicity

    3.21.4) ANIMAL STUDIES
    A) NEOPLASM
    1) RTECS (1999) reports alpha-chloralose to be tumorigenic in mice following a TDLo subcutaneous dose of 215 mg/kg. Tumors of the lung, thorax, or respiratory system and blood were produced.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor vital signs and pulse oximetry in all symptomatic patients.
    B) Monitor for signs of CNS and respiratory depression.
    C) Monitor EEG for seizure activity.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Monitor serum electrolytes, BUN, creatinine, and creatine kinase to assess for rhabdomyolysis, renal dysfunction, and serum chemical abnormalities in patients with coma or seizures.
    4.1.3) URINE
    A) URINALYSIS
    1) Monitor urine analysis and urine output to assess for rhabdomyolysis or renal dysfunction in patients with coma or seizures.
    4.1.4) OTHER
    A) OTHER
    1) MONITORING
    a) If respiratory tract irritation is present, monitor arterial blood gases and chest x-ray.
    2) OXYGEN SATURATION
    a) Monitor pulse oximetry and arterial blood gases in all symptomatic patients.

Methods

    A) CHROMATOGRAPHY
    1) Kintz et al (1996) described a head space capillary gas chromatography method, using a Perkin Elmer GC 9000 HS40 chromatograph and a flame ionization detector, to quantitate plasma and urine levels of chloralose. Detection limits were 0.5 mg/L. Kintz et al (1999) described a newer method using headspace-GC/MS for quantification of alpha-chloralose in body fluids and tissues of a post-mortem case.
    a) Schmid & Iten (1994) described a similar procedure for detection of chloralose in the body fluids of a fatality.
    2) Thomas et al (1988) reported a gas chromatography method using trimethylsilyl derivatization and electron capture detection to measure the concentration of free chloralose in plasma and urine.
    B) SPECTROSCOPY
    1) (1)H nuclear magnetic resonance ((1)H NMR) spectroscopy was used to measure alpha chloralose in biological fluids following intentional exposure in two adults. The authors noted that this method was easy to perform and that analysis of chloralose in urine by either GC-MS or (1)H NMR spectroscopy were comparable (Savin et al, 2003).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Monitor vital signs and pulse oximetry in all symptomatic patients.
    B) Monitor for signs of CNS and respiratory depression.
    C) Monitor EEG for seizure activity.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) EMESIS/NOT RECOMMENDED
    1) Rapid absorption may result in deep stupor or coma within 30 to 60 minutes and/or seizures (Quinio et al, 1995; Thomas et al, 1988).
    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) Inducing emesis should be AVOIDED.
    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) MONITORING OF PATIENT
    1) The following parameters should be monitored frequently:
    a) Vital signs including temperature and respirations.
    b) Arterial blood gases to assess acid-base status and pulmonary/respiratory function.
    c) Serum electrolytes, BUN, creatinine, and creatine kinase, urine analysis and urine output to assess for rhabdomyolysis, renal dysfunction, and serum chemical abnormalities in patients with coma or seizures.
    B) 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).
    7) PROPOFOL - has been used for generalized myoclonic seizures, refractory to benzodiazepines (Quinio et al, 1995). Quinio et al (1995) reported refractory seizures in a patient who had had a cumulative dose of 140 mg of diazepam over 3 hours. Diazepam was stopped, and a loading dose of propofol (100 mg) was given within 1 minute, followed by an infusion of 1 mg/kg/hr, with no further seizure activity reported. Propofol was stopped after 5 hours.
    8) RECURRING SEIZURES
    a) If seizures are not controlled by the above measures, patients will require endotracheal intubation, mechanical ventilation, continuous EEG monitoring, a continuous infusion of an anticonvulsant, and may require neuromuscular paralysis and vasopressor support. Consider continuous infusions of the following agents:
    1) MIDAZOLAM: ADULT DOSE: An initial dose of 0.2 mg/kg slow bolus, at an infusion rate of 2 mg/minute; maintenance doses of 0.05 to 2 mg/kg/hour continuous infusion dosing, titrated to EEG (Brophy et al, 2012). PEDIATRIC DOSE: 0.1 to 0.3 mg/kg followed by a continuous infusion starting at 1 mcg/kg/minute, titrated upwards every 5 minutes as needed (Loddenkemper & Goodkin, 2011).
    2) PROPOFOL: ADULT DOSE: Start at 20 mcg/kg/min with 1 to 2 mg/kg loading dose; maintenance doses of 30 to 200 mcg/kg/minute continuous infusion dosing, titrated to EEG; caution with high doses greater than 80 mcg/kg/minute in adults for extended periods of time (ie, longer than 48 hours) (Brophy et al, 2012); PEDIATRIC DOSE: IV loading dose of up to 2 mg/kg; maintenance doses of 2 to 5 mg/kg/hour may be used in older adolescents; avoid doses of 5 mg/kg/hour over prolonged periods because of propofol infusion syndrome (Loddenkemper & Goodkin, 2011); caution with high doses greater than 65 mcg/kg/min in children for extended periods of time; contraindicated in small children (Brophy et al, 2012).
    3) PENTOBARBITAL: ADULT DOSE: A loading dose of 5 to 15 mg/kg at an infusion rate of 50 mg/minute or lower; may administer additional 5 to 10 mg/kg. Maintenance dose of 0.5 to 5 mg/kg/hour continuous infusion dosing, titrated to EEG (Brophy et al, 2012). PEDIATRIC DOSE: A loading dose of 3 to 15 mg/kg followed by a maintenance dose of 1 to 5 mg/kg/hour (Loddenkemper & Goodkin, 2011).
    4) THIOPENTAL: ADULT DOSE: 2 to 7 mg/kg, at an infusion rate of 50 mg/minute or lower. Maintenance dose of 0.5 to 5 mg/kg/hour continuous infusing dosing, titrated to EEG (Brophy et al, 2012)
    b) Endotracheal intubation, mechanical ventilation, and vasopressors will be required (Brophy et al, 2012) and consultation with a neurologist is strongly advised.
    c) Neuromuscular paralysis (eg, rocuronium bromide, a short-acting nondepolarizing agent) may be required to avoid hyperthermia, severe acidosis, and rhabdomyolysis. If rhabdomyolysis is possible, avoid succinylcholine chloride, because of the risk of hyperkalemic-induced cardiac dysrhythmias. Continuous EEG monitoring is mandatory if neuromuscular paralysis is used (Manno, 2003).
    C) AIRWAY MANAGEMENT
    1) In cases of airway compromise, supportive measures including endotracheal intubation and mechanical ventilation may be necessary secondary to chloralose induced CNS depression resulting in respiratory failure.
    2) Atropine has been used to treat the tracheobronchial hypersecretory state that can occur following overdose (Savin et al, 2003).
    D) 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).
    E) ACUTE LUNG INJURY
    1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
    2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).
    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)
    3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
    4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
    5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
    6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
    7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).
    F) RHABDOMYOLYSIS
    1) SUMMARY: Early aggressive fluid replacement is the mainstay of therapy and may help prevent renal insufficiency. Diuretics such as mannitol or furosemide may be added if necessary to maintain urine output but only after volume status has been restored as hypovolemia will increase renal tubular damage. Urinary alkalinization is NOT routinely recommended.
    2) Initial treatment should be directed towards controlling acute metabolic disturbances such as hyperkalemia, hyperthermia, and hypovolemia. Control seizures, agitation, and muscle contractions (Erdman & Dart, 2004).
    3) FLUID REPLACEMENT: Early and aggressive fluid replacement is the mainstay of therapy to prevent renal failure. Vigorous fluid replacement with 0.9% saline (10 to 15 mL/kg/hour) is necessary even if there is no evidence of dehydration. Several liters of fluid may be needed within the first 24 hours (Walter & Catenacci, 2008; Camp, 2009; Huerta-Alardin et al, 2005; Criddle, 2003; Polderman, 2004). Hypovolemia, increased insensible losses, and third spacing of fluid commonly increase fluid requirements. Strive to maintain a urine output of at least 1 to 2 mL/kg/hour (or greater than 150 to 300 mL/hour) (Walter & Catenacci, 2008; Camp, 2009; Erdman & Dart, 2004; Criddle, 2003). To maintain a urine output this high, 500 to 1000 mL of fluid per hour may be required (Criddle, 2003). Monitor fluid input and urine output, plus insensible losses. Monitor for evidence of fluid overload and compartment syndrome; monitor serum electrolytes, CK, and renal function tests.
    4) DIURETICS: Diuretics (eg, mannitol or furosemide) may be needed to ensure adequate urine output and to prevent acute renal failure when used in combination with aggressive fluid therapy. Loop diuretics increase tubular flow and decrease deposition of myoglobin. These agents should be used only after volume status has been restored, as hypovolemia will increase renal tubular damage. If the patient is maintaining adequate urine output, loop diuretics are not necessary (Vanholder et al, 2000).
    5) URINARY ALKALINIZATION: Alkalinization of the urine is not routinely recommended, as it has never been documented to reduce nephrotoxicity, and may cause complications such as hypocalcemia and hypokalemia (Walter & Catenacci, 2008; Huerta-Alardin et al, 2005; Brown et al, 2004; Polderman, 2004). Retrospective studies have failed to demonstrate any clinical benefit from the use of urinary alkalinization (Brown et al, 2004; Polderman, 2004; Homsi et al, 1997).

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.
    6.7.2) TREATMENT
    A) IRRITATION SYMPTOM
    1) If respiratory tract irritation or respiratory depression is evident, monitor arterial blood gases, chest x-ray, and pulmonary function tests.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    6.9.2) TREATMENT
    A) IRRITATION SYMPTOM
    1) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

    A) SUMMARY
    1) There is no data regarding the use of hemodialysis, hemoperfusion or diuresis in the management of chloralose poisonings.

Range Of Toxicity

Summary

    A) The oral toxic dose in humans is reported to be 1 to 4 grams. A toxic dose in infants is reported to be 20 mg/kg.
    B) Severe toxicity (coma, seizures, myoclonus, hypothermia, hyperthermia, respiratory failure, metabolic acidosis, rhabdomyolysis) with ultimate survival with aggressive supportive care has been reported after ingestions of up to 30 grams by adults.

Therapeutic Dose

    7.2.1) ADULT
    A) ROUTE OF ADMINISTRATION
    1) ORAL - Prior to 1980, alpha-chloralose was used in Europe as a hypnotic agent in adults in a dose of 250 milligrams (Shita et al, 1981). It is no longer available as a human drug, but is available as a rodenticide as well as a veterinary anesthetic (Thomas et al, 1988; JEF Reynolds , 1999).

Minimum Lethal Exposure

    A) ADULT
    1) Following the ingestion of an unknown amount of a rodenticide containing 5% alpha chloralose, a 67-year-old woman was discovered dead 2 to 3 days later (pp 140-141).
    2) CASE REPORT: A 24-year-old man was found pulseless with several opened packages of medications in his bedroom, including chlorpromazine, pantoprazole, and mesterolone, as well as an empty bottle that contained chloralose 50 g, sold in Italy as a rodenticide. The patient was pronounced dead after 30 minutes of unsuccessful resuscitative measures by emergency personnel. An autopsy revealed general pulmonary edema and multi-visceral congestion, and the presence of chloralose was confirmed in all post-mortem specimens (Gerace et al, 2012).

Maximum Tolerated Exposure

    A) ADULT
    1) A human adult toxic dose is reported to be 1 to 4 grams (Shita et al, 1981; Thomas et al, 1988).
    2) CASE REPORT: An 18-year-old woman survived an oral dose of 10 grams (toxic human dose reported to be 1 to 4 grams). Approximately 2 hours following the overdose, she was found comatose and cyanotic, with intermittent tonic-clonic movements and oculogyric eye movements. Four to five grand mal seizures were reported after hospital admission. EEG showed a slowed delta-wave rhythm. She recovered after 48 hours following symptomatic therapy (Shita et al, 1981).
    3) CASE REPORT: A 70-year-old woman was treated symptomatically for myoclonic seizures following ingestion of 20 grams of chloralose in a suicide attempt. Propofol added to her diazepam treatment resolved seizures and she was discharged from the intensive care unit after 25 hours (Quinio et al, 1995).
    4) CASE SERIES: In a series of 17 cases, estimated chloralose doses ranged from 3 to 30 grams. All patients survived following symptomatic care (Flesch et al, 2000).
    5) CASE SERIES: Symptoms reported in a case series of 49 poisonings, in which all victims survived, are reported as follows (Flesch et al, 2000)
    1) Coma 94%
    2) Myoclonus 92%
    3) Seizures 14%
    4) Respiratory failure 77%
    5) Bronchial secretions 32%
    6) Hypothermia 25%
    7) Hyperthermia 44%
    B) INFANT
    1) A toxic dose in infants is reported to be 20 milligrams/kilogram (Thomas et al, 1988).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) ACUTE
    a) A fatal poisoning with chloralose has been reported, in which the peripheral blood concentration was 410 milligrams/liter (Kintz et al, 1996).
    b) In another fatality due to chloralose, a postmortem femoral blood concentration of 151.3 milligrams/liter was reported (Kintz et al, 1996).
    c) Kintz et al (1999) reported a postmortem peripheral blood concentration of 175.7 milligrams/liter in an 18-year-old male.
    d) In four adult poisonings with chloralose, plasma levels in these survivors ranged from 13.7 to 41.3 milligrams/liter (Kintz et al, 1996).
    e) Head-space gas chromatography revealed a blood and urine concentration of 96.9 milligrams/liter and 41.8 milligrams/liter, respectively, following an ingestion (Flesch et al, 2000).
    f) A 10-year-old boy was reported to have blood and urine levels of 15.2 milligrams/liter and 65 milligrams/liter, respectively, approximately 5 hours post-ingestion of a rodenticide containing 80% alpha-chloralose (Rambourg-Schepens et al, 1999). He experienced generalized seizures following the ingestion.

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) ANIMAL DATA
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 175 mg/kg (RTECS , 1999)
    2) LD50- (ORAL)MOUSE:
    a) 200 mg/kg (RTECS , 1999)
    b) 300 mg/kg (Cornwell, 1969)
    3) LD50- (ORAL)RAT:
    a) 400 mg/kg (RTECS , 1999; Cornwell, 1969)

Pharmacology Toxicology

Toxicologic Mechanism

    A) Alpha chloralose is reported to have a depressant action on the central nervous system and, like strychnine, it also has a stimulant action on spinal reflexes resulting in spontaneous myoclonic jerks and generalized seizure activity in response to peripheral stimulation (Thomas et al, 1988; (Lees, 1972). Dose levels appear to effect the stimulant or depressive actions, with increasing doses resulting in CNS depression (Manzo et al, 1979). Fatalities are due to depression of the CNS.
    1) ANESTHETIC - It has been postulated that selective depressing of inter-neurones in the ascending reticular formation occurs, thus suppressing normal arousal response (Lees, 1972).
    2) STIMULANT - Myoclonic activity or spontaneous jerks occur in the pre-anesthetic stage of poisonings. Generalized seizures occur in lightly anesthetized rodents in response to peripheral sensory stimuli, which ceases in deep anesthesia (Lees, 1972).

Physicochemical

Physical Characteristics

    A) Alpha-chloralose is a white, crystalline, odorless solid prepared from anhydrous glucose and trichloroacetaldehyde (anhydrous chloral) (Budavari, 1996). Technical grade chloralose resembles milk powder (Thomas et al, 1988). It is stable under normal temperatures and pressures. It is incompatible with strong oxidizing agents, strong acids and strong bases (Budavari, 1996; MSDS (Material Safety Data Sheet), 1997).

Ph

    A) 6.8 (MSDS (Material Safety Data Sheet), 1997)

Molecular Weight

    A) 309.53 (Budavari, 1996)

References

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