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BARBITURATES-SHORT ACTING

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Short-acting barbiturates are highly lipid soluble agents which can depress the CNS to produce hypnosis and anesthesia without analgesia.

Specific Substances

    A) CONSTITUENTS OF THE GROUP
    1) ULTRA SHORT ACTING
    a) Methohexital (Brevital) (synonym)
    b) Thiamylal (Surital) (synonym)
    c) Thiopental (Pentothal) (synonym)
    2) SHORT ACTING
    a) Hexobarbital (Evipal) (synonym)
    b) Pentobarbital (Nembutal) (synonym)
    c) Secobarbital (Seconal) (synonym)
    3) INTERMEDIATE ACTING
    a) Butabarbital (Buticaps, Butisol, Barbased, Butolan) (synonym)

Available Forms Sources

    A) FORMS
    1) REPRESENTATIVE DRUGS
    a) Allobarbitone (de Boer et al, 1989)
    b) Butalbital
    c) Cyclobarbitone
    d) Heptabarbitone
    e) Hexobarbitone
    f) Pentobarbitone
    g) Secobarbital (Quinalbarbitone)
    h) Thiopentone
    2) COMBINATION PRODUCTS: Short acting barbiturates are also available in combination with other agents such as analgesics and antimigraine drugs:
    1) Analgesics: Esgic and Fioricet (Butalbital, caffeine, and acetaminophen)
    2) Antimigraine preparations: Cafergot tablets and suppositories (Pentobarbital with ergotamine tartarate, caffeine, and belladona alkaloids)
    3) VETERINARY EUTHANASIA AGENTS
    BRAND NAME(R)MANUFACTURERINGREDIENTS*
    Beuthanasia-DBurns-Biotec390 mg/mL pentobarbital 50 mg/mL phenytoin
    Euthanasia solMed-Tech325 mg/mL pentobarbital
    FatalN Am Pharmacal325 mg/mL pentobarbital
    LethalEli Lilly260 mg/mL pentobarbital
    ReposeDiamond400 mg/mL secobarbital 50 mg mephenesin
    SleepawayFt Dodge260 mg/mL pentobarbital
    SocumbThe Butler Co360 mg/mL pentobarbital
    T-61Amer Hoechst200 mg/mL embutramide 50 mg/mL mebezonium 5 mg/mL tetracaine
    * May also contain propylene glycol up to 20 percent; polyethylene glycol up to 20 percent; and alcohol up to 31 percent. Reference: Cordell et al, 1986

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Sedative hypnotics used for sedation and treatment of epilepsy, including status epilepticus. Most short acting barbiturates including methohexital, thiopental, hexobarbital, pentobarbital, are intravenous medication; secobarbital and butabarbital are administered orally. Short-acting barbiturates may be abused recreationally and have many different "street names".
    B) EPIDEMIOLOGY: Poisoning is uncommon, as benzodiazepines and newer anticonvulsants have taken the place of most of the historical uses of barbiturates. However, toxicity may be severe and may occur via oral or parenteral routes.
    C) PHARMACOLOGY: Barbiturates cause depression of neuronal activity via alteration of gamma-aminobutyric acid (GABA) mediated chlorine currents. Specifically, barbiturates increase the duration of opening of the chlorine ionophore.
    D) TOXICOLOGY: It is an extension of the pharmacologic effects. Central nervous system depression is the primary effect and may be accompanied by hypotension secondary to direct myocardial depression. Poisoning may be exacerbated by co-ingestion of other sedatives.
    E) WITH THERAPEUTIC USE
    1) ADVERSE EFFECTS: Mild sedation, dizziness, impaired coordination may develop in some patients.
    F) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Somnolence, slurred speech, nystagmus, confusion, and ataxia may occur.
    2) SEVERE TOXICITY: Severe effects may include coma, hypotension, decreased myocardial contractility, hypothermia and respiratory depression. Hypoglycemia has been reported in a substantial number of patients. Blisters ("barb-burns") may occur secondary to prolonged immobilization from coma, but are not specific to barbiturate intoxication. Patients may have small to midpoint pupils and have very diminished reflexes. Death is most commonly caused by respiratory depression and cardiovascular collapse. Patients that present after prolonged coma are at risk for aspiration pneumonia, rhabdomyolysis and renal failure. Fatalities are extremely rare if early respiratory support is provided.
    0.2.3) VITAL SIGNS
    A) WITH POISONING/EXPOSURE
    1) Hypothermia and hypotension are common following barbiturate intoxications.
    0.2.20) REPRODUCTIVE
    A) Methohexital has been classified as FDA pregnancy category B, Aspirin/butalbital/caffeine, butalbital/acetaminophen/caffeine/codeine phosphate, butalbital/aspirin/caffeine/codeine phosphate, and thiopental have been classified as FDA pregnancy category C. Amobarbital, butabarbital, pentobarbital, and secobarbital have been classified as FDA pregnancy category D. The use of barbiturates by pregnant woman may result in fetal harm. These agents can readily cross the placenta and are distributed in fetal tissues.

Laboratory Monitoring

    A) Monitor vital signs and mental status.
    B) Short-acting barbiturates may be detected on urine immunoassays, usually for less than 2 days after ingestion.
    C) Specific serum drug levels may be available in the hospital laboratory, but are not useful for guiding therapy. Toxic levels for methohexital and thiopental are greater than 5 mg/L. Pentobarbital and secobarbital levels greater than 10 mg/L may be toxic.
    D) Obtain an ECG and institute continuous cardiac monitoring in patients with moderate to severe toxicity.
    E) Monitor creatinine phosphokinase in patients with prolonged immobilization from coma; monitor renal function and urine output in patients with rhabdomyolysis.
    F) Routine monitoring of electrolytes, renal function, glucose, pulse oximetry and blood gases may be helpful. Other causes of coma and hypotension should be ruled out.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Activated charcoal may be given if a patient presents shortly after ingestion, and are awake and alert with a protected airway.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Orotracheal intubation for airway protection should be performed if patient is increasingly drowsy or comatose. Administer activated charcoal if recent ingestion (GI decontamination should only be performed in patients who can protect their airway or who are intubated). Severe hypotension and hypothermia may develop and require rewarming, intravenous normal saline, and in some cases vasopressors. Tetanus and routine wound care for blisters. A burn surgeon should be consulted for extensive skin blistering.
    C) DECONTAMINATION
    1) PREHOSPITAL: Not recommended because of the potential for somnolence and loss of airway protection.
    2) HOSPITAL: Activated charcoal if recent, substantial ingestion, and patient able to protect airway.
    D) AIRWAY MANAGEMENT
    1) Perform early in patients with severe intoxication (significant CNS depression, coma, respiratory depression or hypotension).
    E) ANTIDOTE
    1) There is no antidote for barbiturates.
    F) HYPOTENSION
    1) Secure intravenous access. Initiate treatment with intravenous fluids. Administer pressors (dopamine, norepinephrine) and titrate to a mean arterial pressure of at least 60 mmHg as indicated. Insert a foley catheter to monitor urine output.
    G) COMA
    1) Treat symptomatically and supportively. Administer oxygen; perform orotracheal intubation to protect airway. Obtain a bedside blood glucose measurement and treat hypoglycemia, if present. Administer naloxone as necessary to treat coincident opioid toxicity.
    H) HYPOTHERMIA
    1) Monitor core temperature with rectal or bladder probe. Initiate external rewarming to include warmed: blankets, IV fluids and humidified oxygen until the temperature is greater than 32.2 degrees Celsius. For severe hypothermia, provide gastric or peritoneal lavage with warm fluids, consider warm fluids via chest tubes, and for very severe cases associated with cardiac arrest, perform rewarming with cardiopulmonary bypass.
    I) BRADYCARDIA
    1) Place on cardiac monitor. Correct hypothermia and hypoxia, if present prior to initiating other treatment(s) for bradycardia. Do not treat sinus bradycardia unless the patient is hypotensive. Follow ACLS protocol including the use of atropine, epinephrine and, if necessary external or internal cardiac pacing.
    J) ENHANCED ELIMINATION
    1) Hemodialysis or hemoperfusion may be considered in patients who do not respond to symptomatic supportive care, although there use has not been proven to be beneficial in patients that have overdosed on short-acting barbiturates. NOTE: Urinary alkalinization is NOT effective for short-acting barbiturates as they are primarily metabolized by the liver with very little excretion by the kidneys and a low acid dissociation constant.
    K) PATIENT DISPOSITION
    1) HOME CRITERIA: Any child that ingests a short-acting barbiturate should be evaluated by a healthcare professional.
    2) OBSERVATION CRITERIA: Patients with deliberate ingestions and symptomatic patients should be sent to a healthcare facility for observation for at least 6 to 8 hours.
    3) ADMISSION CRITERIA: Patients with significant persistent central nervous system toxicity (i.e., CNS depression, confusion, or ataxia) should be admitted. Patients with coma, hypotension, respiratory depression or hypothermia should be admitted to an intensive care setting.
    4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity (i.e., coma, respiratory depression, hypotension or hypothermia) or in whom the diagnosis is not clear.
    L) PITFALLS
    1) Failure to diagnose other causes of coma.
    M) PHARMACOKINETICS
    1) Generally, rapid absorption. Onset of action is usually 15 to 30 minutes for short-acting barbiturates; ultra-fast acting has an onset of one minute or less following intravenous administration and 2 to 10 minutes following intramuscular administration; and intermediate-acting has an onset of 45 to 60 minutes. Short-acting barbiturates are primarily metabolized in the liver with renal excretion of metabolites, but little excretion of the parent drug. Short-acting barbiturates can accelerate their own hepatic metabolism by autoinduction.
    N) DIFFERENTIAL DIAGNOSIS
    1) Ethanol/benzodiazepine/long-acting barbiturate/opioid/other sedative-hypnotic or anticonvulsant poisoning, carbon monoxide or cyanide poisoning, hypoglycemia, infection, environmental hypothermia, metabolic derangement, biogenic amine syndrome (cocaine or methamphetamine washout), stroke or hypothyroidism.

Range Of Toxicity

    A) The toxic dose varies depending on route and speed of administration as well as patient tolerance. GENERAL: Toxic levels for methohexital and thiopental are greater than 5 mg/L. Pentobarbital and secobarbital levels greater than 10 mg/L may be toxic. ADULT: 100 mg will cause sleepiness. Fatalities have occurred after 2 to 10 grams of pentobarbital or as little as 2 grams of secobarbital. PEDIATRIC: 3 to 5 mg/kg of most short acting barbiturates may cause some symptoms. Doses exceeding 5 to 8 mg/kg may require clinical intervention in children.

Clinical Effects

Summary Of Exposure

    A) USES: Sedative hypnotics used for sedation and treatment of epilepsy, including status epilepticus. Most short acting barbiturates including methohexital, thiopental, hexobarbital, pentobarbital, are intravenous medication; secobarbital and butabarbital are administered orally. Short-acting barbiturates may be abused recreationally and have many different "street names".
    B) EPIDEMIOLOGY: Poisoning is uncommon, as benzodiazepines and newer anticonvulsants have taken the place of most of the historical uses of barbiturates. However, toxicity may be severe and may occur via oral or parenteral routes.
    C) PHARMACOLOGY: Barbiturates cause depression of neuronal activity via alteration of gamma-aminobutyric acid (GABA) mediated chlorine currents. Specifically, barbiturates increase the duration of opening of the chlorine ionophore.
    D) TOXICOLOGY: It is an extension of the pharmacologic effects. Central nervous system depression is the primary effect and may be accompanied by hypotension secondary to direct myocardial depression. Poisoning may be exacerbated by co-ingestion of other sedatives.
    E) WITH THERAPEUTIC USE
    1) ADVERSE EFFECTS: Mild sedation, dizziness, impaired coordination may develop in some patients.
    F) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Somnolence, slurred speech, nystagmus, confusion, and ataxia may occur.
    2) SEVERE TOXICITY: Severe effects may include coma, hypotension, decreased myocardial contractility, hypothermia and respiratory depression. Hypoglycemia has been reported in a substantial number of patients. Blisters ("barb-burns") may occur secondary to prolonged immobilization from coma, but are not specific to barbiturate intoxication. Patients may have small to midpoint pupils and have very diminished reflexes. Death is most commonly caused by respiratory depression and cardiovascular collapse. Patients that present after prolonged coma are at risk for aspiration pneumonia, rhabdomyolysis and renal failure. Fatalities are extremely rare if early respiratory support is provided.

Vital Signs

    3.3.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Hypothermia and hypotension are common following barbiturate intoxications.
    3.3.3) TEMPERATURE
    A) WITH POISONING/EXPOSURE
    1) Hypothermia is a common occurrence following barbiturate intoxications (Crellin et al, 2015; Prod Info NEMBUTAL(R) intramuscular, intravenous solution, 2005; McCarron et al, 1982; Fell, 1968; Lash, 1967; Clark & Sumerling, 1966).
    3.3.4) BLOOD PRESSURE
    A) WITH POISONING/EXPOSURE
    1) Hypotension is a common finding following a barbiturate overdose (Crellin et al, 2015; Prod Info NEMBUTAL(R) intramuscular, intravenous solution, 2005).

Heent

    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) Nystagmus is a common finding of acute barbiturate intoxication (Prod Info NEMBUTAL(R) intramuscular, intravenous solution, 2005).
    3.4.6) THROAT
    A) WITH POISONING/EXPOSURE
    1) STOMATITIS ULCERATIVE: Necrotic ulcers were reported in the oral mucosa and on the cutaneous counterpart of the chin of a man who took approximately 100 mg secobarbital orally in a suicide attempt. The ulcers appeared within ten days of the ingestion and required 9 weeks to heal fully (Monteil et al, 1991).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) Hypotension may occur. Hypotension may also result from hypersensitivity, most commonly after intravenous injection (Cordell et al, 1986; Harle et al, 1986).
    b) Marked hypotension occurred in 8 of 10 asphyxiated newborns treated with thiopental with mean serum concentration of 13.4 micrograms per milliliter (Garg et al, 1988).
    c) CASE REPORT: Bradycardia (46 beats/min) and hypotension (99/53 mmHg) were reported in a 48-year-old woman following intentional injection of a combination veterinary medication containing 390 mg/mL pentobarbital and 50 mg/mL phenytoin. Serum pentobarbital and phenytoin concentrations were 12.6 mcg/mL (reference range 1 to 5 mcg/mL) and 2.5 mcg/mL (reference range 10 to 20 mcg/mL), respectively (Crellin et al, 2015).
    B) SHOCK
    1) WITH POISONING/EXPOSURE
    a) Acute barbiturate overdose can result in a "shock syndrome" which can include: circulatory collapse, apnea, respiratory arrest and death (Prod Info NEMBUTAL(R) intramuscular, intravenous solution, 2005).
    C) BRADYCARDIA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Bradycardia (46 beats/min) and hypotension (99/53 mmHg) were reported in a 48-year-old woman following intentional injection of a combination veterinary medication containing 390 mg/mL pentobarbital and 50 mg/mL phenytoin. Serum pentobarbital and phenytoin concentrations were 12.6 mcg/mL (reference range 1 to 5 mcg/mL) and 2.5 mcg/mL (reference range 10 to 20 mcg/mL), respectively (Crellin et al, 2015).
    D) CARDIAC ARREST
    1) WITH POISONING/EXPOSURE
    a) Peripheral vascular collapse and cardiac arrest may occur following overdoses (Cordell et al, 1986; Fell, 1968).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) APNEA
    1) WITH POISONING/EXPOSURE
    a) Respiratory failure including apnea and respiratory arrest may occur following an acute overdose (Crellin et al, 2015; Prod Info NEMBUTAL(R) intramuscular, intravenous solution, 2005; McCarron et al, 1982; Cordell et al, 1986).
    B) PULMONARY ASPIRATION
    1) WITH POISONING/EXPOSURE
    a) Aspiration pneumonia has been reported, in barbiturate ingestions, following vomiting of gastric contents (Clark & Sumerling, 1966; McCarron et al, 1982; Cordell et al, 1986).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM FINDING
    1) WITH POISONING/EXPOSURE
    a) Acute intoxication primarily results in central nervous system and respiratory depression (Prod Info NEMBUTAL(R) intramuscular, intravenous solution, 2005).
    b) Unsteady gait, slurred speech and sustained nystagmus are common symptoms of acute barbiturate intoxication. Common findings of chronic intoxication are confusion, poor judgement, irritability and insomnia (Prod Info NEMBUTAL(R) intramuscular, intravenous solution, 2005).
    B) COMA
    1) WITH POISONING/EXPOSURE
    a) Any sedative-hypnotic drug enhances the toxic actions of barbiturates. Toxic effects include profound shock, lowered body temperature, and coma (Prod Info NEMBUTAL(R) intramuscular, intravenous solution, 2005; Clark & Sumerling, 1966; McCarron et al, 1982; Cordell et al, 1986).
    b) CASE REPORT: A 48-year-old woman was found unresponsive (Glasgow Coma Scale of 3), apneic, and hypoxemic next to a syringe containing pink fluid that had been injected into her left antecubital fossa. She was bradycardic (46 beats/min) and hypotensive (99/53 mmHg), with a room air pulse oximetry of 78%. Physical examination indicated left forearm compartment syndrome. Laboratory data revealed a serum creatine phosphokinase concentration of 806 units/L. The pink fluid within the syringe was identified as a combination medication consisting of 390 mg/mL pentobarbital and 50 mg/mL phenytoin. Subsequently, serum pentobarbital and phenytoin concentrations were measured as 12.6 mcg/mL (reference range 1 to 5 mcg/mL) and 2.5 mcg/mL (reference range 10 to 20 mcg/mL), respectively. With supportive care and fasciotomy to treat the compartment syndrome, the patient recovered without neurologic sequelae (Crellin et al, 2015).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) CRUSH SYNDROME
    1) WITH POISONING/EXPOSURE
    a) Acute tubular necrosis, confirmed by renal biopsy, was reported in a 35-year-old male following an overdose of pentobarbitone complicated by rhabdomyolysis and hypotension. The patient recovered with supportive care (Clark & Sumerling, 1966).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) BULLOUS ERUPTION
    1) WITH POISONING/EXPOSURE
    a) Erythematous or hemorrhagic blisters occur in various areas of the body, most typically on the hands, buttocks, between the knees, and at any pressure point (Leavell, 1969; Clark & Sumerling, 1966).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) NECROSIS
    1) WITH POISONING/EXPOSURE
    a) Muscle necrosis and calcification occurred in a 35-year-old male following a pentobarbitone overdose. The patient recovered with supportive care (Clark & Sumerling, 1966).
    B) COMPARTMENT SYNDROME
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 48-year-old woman was found unresponsive (Glasgow Coma Scale of 3), apneic, and hypoxemic next to a syringe containing pink fluid that had been injected into her left antecubital fossa. She was bradycardic (46 beats/min) and hypotensive (99/53 mmHg), with a room air pulse oximetry of 78%. Physical examination indicated left forearm compartment syndrome. Laboratory data revealed a serum creatine phosphokinase concentration of 806 units/L. The pink fluid within the syringe was identified as a combination medication consisting of 390 mg/mL pentobarbital and 50 mg/mL phenytoin. Subsequently, serum pentobarbital and phenytoin concentrations were measured as 12.6 mcg/mL (reference range 1 to 5 mcg/mL) and 2.5 mcg/mL (reference range 10 to 20 mcg/mL), respectively. With supportive care and fasciotomy to treat the compartment syndrome, the patient recovered without neurologic sequelae (Crellin et al, 2015).

Endocrine

    3.16.2) CLINICAL EFFECTS
    A) HYPOGLYCEMIA
    1) WITH POISONING/EXPOSURE
    a) INCIDENCE: Hypoglycemia was reported in 22.3% of patients (n=494) following intoxication of single short-acting barbiturates (McCarron et al, 1982).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) ANAPHYLACTOID REACTION
    1) WITH THERAPEUTIC USE
    a) Three cases of anaphylactoid reactions to thiopentone have been reported. All three patients had no history of anaphylactic reactions and were given therapeutic doses of thiopentone for anesthesia. All three patients tested positive on intradermal and prick tests and had IgE specific for thiopentone (Fisher et al, 1989).
    b) Hypersensitivity may present as a rash with or without hypotension; this occurs most commonly following intravenous injection.

Reproductive

    3.20.1) SUMMARY
    A) Methohexital has been classified as FDA pregnancy category B, Aspirin/butalbital/caffeine, butalbital/acetaminophen/caffeine/codeine phosphate, butalbital/aspirin/caffeine/codeine phosphate, and thiopental have been classified as FDA pregnancy category C. Amobarbital, butabarbital, pentobarbital, and secobarbital have been classified as FDA pregnancy category D. The use of barbiturates by pregnant woman may result in fetal harm. These agents can readily cross the placenta and are distributed in fetal tissues.
    3.20.3) EFFECTS IN PREGNANCY
    A) SUMMARY
    1) In general, the use of barbiturates by pregnant woman may result in fetal harm. In retrospective, case-controlled studies, maternal use of barbiturates has suggested a higher than expected incidence of fetal abnormalities. These agents can readily cross the placenta and are distributed in fetal tissues (highest concentrations: placenta, fetal liver and brain). Following parenteral administration, fetal blood levels can reach maternal blood levels (Prod Info SECONAL SODIUM(R) oral capsules, 2006).
    B) BUTALBITAL
    1) Exposure to medications containing butalbital in infants during the periconceptional period resulted in an statistically significant increase in the odds of developing congenital heart defects, including tetralogy of Fallot, pulmonary valve stenosis, or secundum-type atrial septal defects (Browne et al, 2014).
    C) WITHDRAWAL SYNDROME
    1) Infants may develop acute withdrawal symptoms (including seizures and hyperirritability) from birth up to 2 weeks after delivery following long-term barbiturate exposure in utero (Prod Info NEMBUTAL(R) intramuscular, intravenous solution, 2005; Prod Info SECONAL SODIUM(R) oral capsules, 2006).
    D) PREGNANCY CATEGORY
    1) The manufacturer has classified the following product as FDA pregnancy category B:
    1) Methohexital (Prod Info BREVITAL(R) SODIUM IM, IV, RC injection, 2008)
    2) The manufacturers have classified the following products as FDA pregnancy category C:
    1) Aspirin/butalbital/caffeine (Prod Info Fiorinal(R) oral capsules, 2007)
    2) Butalbital/acetaminophen/caffeine/codeine phosphate (Prod Info Fioricet(R) with Codeine C-III oral capsules, 2011)
    3) Butalbital/aspirin/caffeine/codeine phosphate (Prod Info Fiorinal(R) with Codeine oral capsule, 2009)
    4) Thiopental (Prod Info PENTOTHAL(R) IV injection, 2004)
    3) The manufacturers have classified the following products as FDA pregnancy category D:
    1) Amobarbital (Prod Info AMYTAL(R) SODIUM injection, 2004)
    2) Butabarbital (Prod Info BUTISOL SODIUM(R)CIII oral tablets, solution, 2007)
    3) Pentobarbital (Prod Info NEMBUTAL(R) intramuscular, intravenous solution, 2005)
    4) Secobarbital (Prod Info SECONAL SODIUM(R) oral capsules, 2006)
    E) ANIMAL STUDIES
    1) METHOHEXITAL SODIUM
    a) RATS, RABBITS: There was no evidence of fetal harm at doses of up to 4 and 7 times the human dose, respectively (Prod Info BREVITAL(R) SODIUM IM, IV, RC injection, 2008).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREASTFEEDING
    1) Small amounts of some barbiturates are excreted in human milk. Caution is advised in nursing mothers who are receiving barbiturates to assess the potential benefits and risks to the infant (Prod Info BREVITAL(R) SODIUM IM, IV, RC injection, 2008; Prod Info SECONAL SODIUM(R) oral capsules, 2006; Prod Info AMYTAL(R) SODIUM injection, 2004; Prod Info NEMBUTAL(R) intramuscular, intravenous solution, 2005).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor vital signs and mental status.
    B) Short-acting barbiturates may be detected on urine immunoassays, usually for less than 2 days after ingestion.
    C) Specific serum drug levels may be available in the hospital laboratory, but are not useful for guiding therapy. Toxic levels for methohexital and thiopental are greater than 5 mg/L. Pentobarbital and secobarbital levels greater than 10 mg/L may be toxic.
    D) Obtain an ECG and institute continuous cardiac monitoring in patients with moderate to severe toxicity.
    E) Monitor creatinine phosphokinase in patients with prolonged immobilization from coma; monitor renal function and urine output in patients with rhabdomyolysis.
    F) Routine monitoring of electrolytes, renal function, glucose, pulse oximetry and blood gases may be helpful. Other causes of coma and hypotension should be ruled out.
    4.1.2) SERUM/BLOOD
    A) TOXICITY
    1) Several investigators have attempted to correlate serum short acting barbiturate concentrations with clinical effects (stage of coma).
    a) The following serum short acting barbiturate levels for healthy, nonaddicted acute overdose patients include (McCarron et al, 1982):
    1) Alert: less than 6 mcg/mL
    2) Stuporous: 11 to 17 mcg/mL
    3) Stage 2 Coma (Not responsive to pain, but stable respiration and circulation): 20 to 24 mcg/mL
    4) Stage 4 Coma (Not responsive to pain with apnea and/or hypotension): 28 to 40 mcg/mL
    2) Patients with chronic and acute upon chronic intoxications may tolerate higher concentrations with less pronounced symptoms (Baxter et al, 1986).
    3) If blood barbiturate concentrations do not agree with observed clinical findings, suspect other additional medical problems (concurrent alcohol or drug ingestion, head injury, aspiration pneumonitis, etc).
    a) Stage of coma and other clinical signs/symptoms are more accurate predictors of severity and outcome than blood levels alone.

Methods

    A) IMMUNOASSAY
    1) Semiquantitative and qualitative EMIT(TM) homogeneous enzyme immunoassays are available for measurement of this class of barbiturates in urine and in serum or plasma.
    a) Drugs detected include secobarbital, amobarbital, butabarbital, pentobarbital, phenobarbital, and talbutal. Assay responses for samples containing more than one barbiturate may be cumulative.
    b) The detection limit (sensitivity) of the semiquantitative urine assay is 2 mcg/mL of secobarbital or its equivalent.
    c) The qualitative urine assay detects as little as 0.5 mcg/mL of secobarbital.
    d) The semiquantitative serum assay measured drug concentrations in the range of 0 to 6 mcg/mL for secobarbital; the qualitative serum assay's detection limit is 6 mcg/mL for secobarbital.
    e) Clinical studies demonstrate that the serum assays have specificity, precision, and accuracy equivalent to GLC. CDC proficiency testing and clinical studies show that the urine assays compare favorably with GC and TLC.
    f) Mefenamic acid interferes with the ability to detect barbiturates using the EMIT(TM) assay (Crane et al, 1993).
    B) CHROMATOGRAPHY
    1) GC/MS method was described for detecting thiamylal with a lower detection limit of 0.01 mcg/g tissue (Kudo et al, 1988).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients with significant persistent central nervous system toxicity (CNS depression, confusion, or ataxia) should be admitted. Patients with coma, hypotension, respiratory depression or hypothermia should be admitted to an intensive care setting.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Any child that ingests a short-acting barbiturate should be evaluated by a healthcare professional.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity (coma, respiratory depression, hypotension or hypothermia) or in whom the diagnosis is not clear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with deliberate ingestions and symptomatic patients should be sent to a healthcare facility for observation for at least 6 to 8 hours
    6.3.2) DISPOSITION/PARENTERAL EXPOSURE
    6.3.2.1) ADMISSION CRITERIA/PARENTERAL
    A) Patients with significant persistent central nervous system toxicity (CNS depression, confusion, or ataxia) should be admitted. Patients with coma, hypotension, respiratory depression or hypothermia should be admitted to an intensive care setting.
    6.3.2.2) HOME CRITERIA/PARENTERAL
    A) Any child that ingests a short-acting barbiturate should be evaluated by a healthcare professional.
    6.3.2.3) CONSULT CRITERIA/PARENTERAL
    A) Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity (coma, respiratory depression, hypotension or hypothermia) or in whom the diagnosis is not clear.
    6.3.2.5) OBSERVATION CRITERIA/PARENTERAL
    A) Patients with deliberate ingestions and symptomatic patients should be sent to a healthcare facility for observation for at least 6 to 8 hours

Monitoring

    A) Monitor vital signs and mental status.
    B) Short-acting barbiturates may be detected on urine immunoassays, usually for less than 2 days after ingestion.
    C) Specific serum drug levels may be available in the hospital laboratory, but are not useful for guiding therapy. Toxic levels for methohexital and thiopental are greater than 5 mg/L. Pentobarbital and secobarbital levels greater than 10 mg/L may be toxic.
    D) Obtain an ECG and institute continuous cardiac monitoring in patients with moderate to severe toxicity.
    E) Monitor creatinine phosphokinase in patients with prolonged immobilization from coma; monitor renal function and urine output in patients with rhabdomyolysis.
    F) Routine monitoring of electrolytes, renal function, glucose, pulse oximetry and blood gases may be helpful. Other causes of coma and hypotension should be ruled out.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) 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) 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.
    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).
    6.5.3) TREATMENT
    A) MONITORING OF PATIENT
    1) Monitor vital signs. Short-acting barbiturates may be detected on urine immunoassays, usually for less than 2 days after ingestion.
    2) Specific serum drug levels may be available in the hospital laboratory, but are not useful for guiding therapy. Toxic levels of methohexital and thiopental are greater than 5 mg/L. Pentobarbital and secobarbital levels greater than 10 mg/L may be toxic.
    3) Obtain an ECG and institute continuous cardiac monitoring in patients with moderate to severe toxicity.
    4) Monitor creatinine phosphokinase in patients with prolonged immobilization from coma; monitor renal function and urine output in patients with rhabdomyolysis.
    5) Routine monitoring of electrolytes, renal function, glucose, pulse oximetry and blood gases may be helpful. Other causes of coma and hypotension should be ruled out.
    B) AIRWAY MANAGEMENT
    1) Perform early in patients with severe intoxication (significant CNS depression, coma, respiratory depression or hypotension).
    C) 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).
    D) HYPOTHERMIA
    1) Monitor core temperature with rectal or bladder probe. Initiate external rewarming to include warmed: blankets, IV fluids and humidified oxygen until the temperature is greater than 32.2 degrees Celsius. For severe hypothermia, provide gastric or peritoneal lavage with warm fluids, consider warm fluids via chest tubes, and for very severe cases associated with cardiac arrest, perform rewarming with cardiopulmonary bypass.
    E) COMA
    1) Treat symptomatically and supportively. Administer oxygen; perform orotracheal intubation to protect airway. Obtain a bedside blood glucose measurement and treat hypoglycemia, if present. Administer naloxone as necessary to treat coincident opioid toxicity.
    F) DRUG WITHDRAWAL
    1) May occur upon termination of the drug in addicted individuals. Usual requirement is for ingestion of 800 to 2200 mg/day for 35 days. Treatment of this withdrawal should be with phenobarbital or the addicted agent.
    2) Initial drug dosage should be 30 milligrams phenobarbital for each 100 milligrams short acting barbiturate, divided into each 6 hour dose per day.
    a) If after administration of the initial phenobarbital withdrawal, symptomatology continues, the dosage may be raised until the patient is comfortable.
    3) Once a stabilizing dosage has been obtained, the patient may be gradually withdrawn on phenobarbital with a decreasing dose over three weeks (Sullivan & Sellers, 1986).
    4) NEONATE: Withdrawal may also occur following delivery of an infant to a mother who has been ingesting or abusing the barbiturates.
    a) Treatment is by administration of phenobarbital 3 to 5 milligrams/kilogram/day in divided doses once daily.
    b) A gradual reduction in dosage over 3 to 4 weeks may then be instituted. Patients may continue to demonstrate jitteriness up to 4 to 6 months of age.

Enhanced Elimination

    A) DIURESIS
    1) Forced diuresis is of no value in the treatment of short acting barbiturate intoxication.
    2) Some earlier studies suggested that as much as 20% of these drugs could be removed by this route. The analytical procedures employed in the estimation of barbiturate resulted in false results and it is clear that enhancement of excretion by this route is not in excess of 2 to 5%.
    B) SUMMARY
    1) Hemodialysis or hemoperfusion may be considered in patients who do not respond to symptomatic supportive care, although there use has not been proven to be beneficial in patients that have overdosed on short-acting barbiturates.
    a) HEMODIALYSIS
    1) Has been reported successful in removing short acting barbiturates to alter the course of the intoxication, but is less effective than hemoperfusion (Winchester et al, 1977).
    2) The efficacy of hemodialysis for the removal of pentobarbital has been questioned, since no evidence of a significant contribution to total body clearance was found (Wermeling et al, 1985).
    b) HEMOPERFUSION
    1) May be helpful in severely poisoned patients with high blood levels (DeBroc, 1986).

Abstracts

Case Reports

    A) SPECIFIC AGENT
    1) THIOPENTONE
    a) A 22-year-old male paramedic was found dead with an intravenous infusion set attached to his left arm. Thiopentone was detected in the infusion set, and his blood thiopentone level was 27.9 mg (Backer, 1975).
    b) A 24-year-old nurse injected thiopentone with a syringe intravenously into the dorsum of her foot and was found dead. Blood thiopentone level was 0.92 mg several hours after death (Noirfalise, 1978).
    c) A 33-year-old male physician was found dead with an empty intravenous infusion set attached to his left arm. Empty bottles, which had contained a total of 25 g thiopentone, were found nearby. His blood thiopentone concentration was 15.3 mg (Fernando, 1990).
    2) VETERINARY EUTHANASIA AGENTS
    a) Veterinary euthanasia agents, most of which contain barbiturates, may be suicide agents in people with access to them.
    b) Three cases were reported, one fatal, in which euthanasia agents were used. These agents are commonly injected or orally ingested and may be fatal either way (Cordell et al, 1986).
    c) A 17-year-old boy was found unresponsive after injecting an unknown amount of pentobarbital euthanasia agent intravenously. He later died; a serum pentobarbital level taken four hours after injection was 30.7 mcg/mL.
    d) A 29-year-old woman was found lethargic with an empty bottle of pentobarbital euthanasia solution nearby. No needle marks were found on her body; she was treated and recovered uneventfully.
    e) A 39-year-old veterinarian was found unresponsive after drinking juice adulterated with pentobarbital and other euthanasia agents. Serum pentobarbital level was 6.1 mcg/mL; the patient was treated and eventually recovered.
    f) A 21-year-old man was found dead with an IV line leading to a bottle of thiamylal, veterinary formulation, in his arm. Postmortem thiamylal blood concentration was 129 mg/L (Stockham et al, 1991).
    3) METHOHEXITAL
    a) Accidental epidural administration of 5 mL of 1% methohexital resulted in prolonged recovery from anesthesia, but no other adverse effects in a 25-year-old woman (Wells et al, 1987).

Range Of Toxicity

Summary

    A) The toxic dose varies depending on route and speed of administration as well as patient tolerance. GENERAL: Toxic levels for methohexital and thiopental are greater than 5 mg/L. Pentobarbital and secobarbital levels greater than 10 mg/L may be toxic. ADULT: 100 mg will cause sleepiness. Fatalities have occurred after 2 to 10 grams of pentobarbital or as little as 2 grams of secobarbital. PEDIATRIC: 3 to 5 mg/kg of most short acting barbiturates may cause some symptoms. Doses exceeding 5 to 8 mg/kg may require clinical intervention in children.

Therapeutic Dose

    7.2.1) ADULT
    A) SPECIFIC SUBSTANCE
    1) SECOBARBITAL
    a) HYPNOTIC: 100 mg orally at bedtime (Prod Info SECONAL SODIUM(R) oral capsules, 2008).
    b) PRE-ANESTHETIC: 200 to 300 mg orally 1 to 2 hours before surgery (Prod Info SECONAL SODIUM(R) oral capsules, 2008).
    B) SPECIFIC SUBSTANCES
    1) AMOBARBITAL
    a) Sedative: The usual dose is 30 to 50 mg given 2 to 3 times daily. It may be given by either the intramuscular (preferred) or the intravenous route. Maximum single dose: 1 gram (Prod Info AMYTAL(R) SODIUM injection, 2004).
    b) Hypnotic: The usual dose is 65 to 200 mg at bedtime. It may be given by either the intramuscular (preferred) or the intravenous route. Maximum single dose: 1 gram (Prod Info AMYTAL(R) SODIUM injection, 2004).
    2) BUTABARBITAL
    a) Daytime sedative: The usual dose is 15 to 30 mg orally 3 to 4 times daily (Prod Info BUTISOL SODIUM(R)CIII oral tablets, solution, 2007)
    b) Bedtime hypnotic: The usual dose is 15 to 100 mg orally daily (Prod Info BUTISOL SODIUM(R)CIII oral tablets, solution, 2007).
    c) Preoperative sedative: The usual dose is 50 to 100 mg orally 60 to 90 minutes prior to surgery (Prod Info BUTISOL SODIUM(R)CIII oral tablets, solution, 2007).
    3) METHOHEXITAL
    a) Induction of anesthesia: Usual dose: Adult: 1 to 1.5 mg/kg intravenous. A 1% solution (10 mg/mL) is prepared and infused at a rate of 1 mL/5 seconds. This dose can provide anesthesia for approximately 5 to 7 minutes (Prod Info BREVITAL(R) SODIUM IM, IV, RC injection, 2008).
    b) Maintenance of anesthesia: Intermittent injection of a 1% solution (10 mg/mL) of approximately 20 to 40 mg (2 to 4 mL of a 1% solution) every 4 to 7 minutes. For a continuous intravenous infusion of a 0.2% solution, the average rate of infusion is about 3 mL (1 drop/second). The rate can be adjusted as necessary (Prod Info BREVITAL(R) SODIUM IM, IV, RC injection, 2008).
    4) PENTOBARBITAL
    a) Hypnotic: 150 to 200 mg as a single intramuscular injection for adults (Prod Info NEMBUTAL(R) intramuscular, intravenous solution, 2005).
    b) Intravenous Route: An initial dose should not exceed 50 mg per minute. In an average adult (70 kg), 100 mg is a common starting dose. Further incremental doses of up 200 to 500 mg may be given to a normal adult (Prod Info NEMBUTAL(R) intramuscular, intravenous solution, 2005).
    5) SECOBARBITAL
    a) Bedtime hypnotic: 100 mg orally at bedtime (Prod Info SECONAL SODIUM(R) oral capsules, 2006)
    b) Preoperative sedative: 200 to 300 mg orally 60 to 120 minutes prior to surgery (Prod Info SECONAL SODIUM(R) oral capsules, 2006)
    6) THIOPENTAL
    a) Induction of anesthesia or anesthetic agent for short (15 minutes) procedures: Thiopental is only given by the intravenous route and by healthcare professionals experienced with intravenous anesthesia. No fixed dose is prescribed because of individual variability. Titrate the dose as indicated; dose is generally proportional to weight (i.e., obese patients usually require a larger dose) (Prod Info PENTOTHAL(R) IV injection, 2004).
    7.2.2) PEDIATRIC
    A) SPECIFIC SUBSTANCE
    1) METHOHEXITONE
    a) Has been administered rectally in children. Sleep was achieved reliably following rectal infusion of 25 to 30 milligrams/kilogram (Forbes et al, 1989).
    2) SECOBARBITAL SODIUM
    a) PRE-ANESTHETIC: 2 to 6 mg/kg; maximum dosage of 100 mg (Prod Info SECONAL SODIUM(R) oral capsules, 2008).
    3) THIOPENTAL SODIUM
    a) GENERAL ANESTHESIA
    1) INDUCTION
    a) Neonates (0- to 14-days-old): 3.4 mg/kg, administered intravenously (Westrin et al, 1989).
    b) Infants (1 to 6 months): 5 to 8 mg/kg, administered intravenously (Westrin et al, 1989).
    c) Children (1 to 12 years): 5 to 6 mg/kg, administered intravenously (Jonmarker et al, 1987).
    2) MAINTENANCE
    a) For maintenance, the usual thiopental dose is 25 to 50 milligrams intermittently injected for children weighing 30 to 50 kilograms (AMA Department of Drugs, 1986).
    4) PENTOBARBITAL
    a) SEDATION-RADIOLOGIC IMAGING
    1) INTRAVENOUS
    a) Infants and children 6 weeks of age and older: Initial dose, 1 to 2.5 mg/kg IV, then titrated to desired effect in 1 to 2 mg/kg increments (Zgleszewski et al, 2008; Pershad et al, 2007; Dalal et al, 2006; Mason et al, 2004; Malviya et al, 2004; Kienstra et al, 2004; Mason et al, 2001; Beebe et al, 2000; Pereira et al, 1993; Strain et al, 1988). Maximum total dose, 6 mg/kg (or 200 mg total dose) (Mason et al, 2001; Beebe et al, 2000).
    2) INTRAMUSCULAR
    a) Children 1 year of age and older: 2 to 6 mg/kg IM; maximum 100 mg (Prod Info NEMBUTAL(R) injection solution, 2005; Pereira et al, 1993; Temme et al, 1990; Strain et al, 1986).
    3) ORAL (IV FORMULATION DILUTED 3:1 IN CHERRY SYRUP)
    a) Infants less than 1 year of age: Initial dose, 4 mg/kg orally approximately 30 minutes prior to procedure; supplemental doses of 2 mg/kg every 30 minutes to a maximum total dose of 8 mg/kg (Mason et al, 2004; Mason et al, 2004a; Rooks et al, 2003; Chung et al, 2000).
    b) STATUS EPILEPTICUS, REFRACTORY (PENTOBARBITAL COMA)
    1) 5 to 10 mg/kg IV loading dose, followed by 1 to 5 mg/kg/hour IV continuous infusion to produce burst-suppression on EEG (Abend & Dlugos, 2008; Yanay et al, 2004; Wheless, 2004; Kim et al, 2001; Claassen et al, 2002; Holmes & Riviello, 1999). One study reports tapering infusion 0.5 mg/kg/hour every 12 hours once patients were seizure-free for a minimum 48 hours (Kim et al, 2001).
    B) BUTABARBITAL
    1) Preoperative sedative: 2 to 6 mg/kg; maximum dose 100 mg (Prod Info BUTISOL SODIUM(R)CIII oral tablets, solution, 2007).
    C) METHOHEXITAL
    1) Induction of anesthesia: The usual dose range via the intramuscular route is 6.6 to 10 mg/kg of a 5% (500 mg diluted in 10 mL) concentration. For rectal administration the usual dose is 25 mg/kg of a 1% solution (10 mg/mL) (Prod Info BREVITAL(R) SODIUM IM, IV, RC injection, 2008).
    D) PENTOBARBITAL
    1) Hypnotic: The recommended pediatric dose is 2 to 6 mg/kg as a single intramuscular injection. The dose should not exceed 100 mg. (Prod Info NEMBUTAL(R) intramuscular, intravenous solution, 2005).
    E) SECOBARBITAL
    1) Preoperative sedative: 2 to 6 mg/kg; maximum dose 100 mg (Prod Info SECONAL SODIUM(R) oral capsules, 2006).

Minimum Lethal Exposure

    A) CASE REPORTS
    1) In 103 fatal cases of secobarbital, reported amounts ingested were as low as 2 grams. Blood concentrations ranged from 5 to 52 micrograms/milliliter (Cravey et al, 1977).
    2) In 61 fatal cases of pentobarbital toxicity, ingested amounts were 2 to 10 grams (Cravey et al, 1977).

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) 3 to 5 milligrams/kilogram of most short acting barbiturates in children may cause some symptomatology and 100 milligrams in adults will cause sleepiness.
    2) Toxicity requiring therapeutic intervention does not usually occur until the dose has exceeded 5 to 8 milligrams/kilogram in children.
    3) Response can be quite variable due to previous exposure to the drug, prior addiction, and usual state of health. Simultaneous ingestion of other depressant agents may also increase the level of coma and depression.
    4) Subjects ingesting 600 milligrams each of pentobarbital and secobarbital (200 milligrams per hour x 3) produced peak levels ranging from 3.4 to 5 micrograms/milliliter (Parker et al, 1970).
    a) These levels were associated with impairment of judgement and alertness, with reaction time and sedation, and with relaxation in the absence of somnolence.
    5) Some patients, particularly chronic users, will not become comatose in the presence of relatively high levels. The fatal dose in a non-addicted adult is estimated at 3 to 6 grams taken at once or over a short period of time.

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) SPECIFIC SUBSTANCE
    a) PENTOBARBITAL
    1) A plasma level of 28 micrograms/milliliter was associated with coma in one patient; he regained consciousness at a level of 13 micrograms/milliliter (Prescott et al, 1973).
    2) In 61 fatalities, postmortem blood concentrations were 5 to 169 micrograms/milliliter (Basalt & Cravey, 1977).
    3) Four hours after intentional injection of an unknown amount of pentobarbital, the serum pentobarbital level was 30.7 micrograms/milliliter (Cordell et al, 1986).
    b) SECOBARBITAL
    1) A 26-year-old man committed suicide by taking secobarbital, nitrazepam and codeine. Postmortem blood levels were as follows: secobarbital, 11.48 micrograms/milliliter; nitrazepam 1.72 micrograms/milliliter; and codeine, 0.036 microgram/milliliter. The codeine concentration was within the reported therapeutic range, but the secobarbital and nitrazepam levels were within the range of previously reported fatal cases (Tracqui et al, 1989).
    2) Coma in nonaddicted adults may occur with levels of 18 mcg/mL. Severe intoxication resulting in respiratory depression and hypotension may occur at levels of 24 mcg/mL and greater.

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) BUTABARBITAL
    1) LD50- (INTRAPERITONEAL)RAT:
    a) 70 mg/kg (RTECS , 2000)
    B) HEXOBARBITAL
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 270 mg/kg (RTECS , 2000)
    2) LD50- (ORAL)MOUSE:
    a) 468 mg/kg (RTECS , 2000)
    3) LD50- (INTRAPERITONEAL)RAT:
    a) 330 mg/kg (RTECS , 2000)
    C) METHOHEXITAL
    D) PENTOBARBITAL
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 75 mg/kg (RTECS , 2000)
    2) LD50- (ORAL)MOUSE:
    a) 170 mg/kg (RTECS , 2000)
    3) LD50- (INTRAPERITONEAL)RAT:
    a) 108 mg/kg (RTECS , 2000)
    4) LD50- (ORAL)RAT:
    a) 125 mg/kg (RTECS , 2000)
    5) LD50- (SUBCUTANEOUS)RAT:
    a) 144 mg/kg (RTECS , 2000)
    E) SECOBARBITAL
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 116 mg/kg (RTECS , 2000)
    2) LD50- (ORAL)MOUSE:
    a) 145 mg/kg (RTECS , 2000)
    F) THIOPENTAL
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 110 mg/kg (RTECS , 2000)
    2) LD50- (ORAL)MOUSE:
    a) 600 mg/kg (RTECS , 2000)
    3) LD50- (SUBCUTANEOUS)MOUSE:
    a) 110 mg/kg (RTECS , 2000)
    4) LD50- (INTRAPERITONEAL)RAT:
    a) 120 mg/kg (RTECS , 2000)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Barbiturates depress the central nervous system but differ widely in dosage, duration of action, and in margin of safety between the therapeutic dose and the toxic dose.
    B) They may be classified according to their clinical duration of action into long, intermediate, and very short acting types.
    C) The short acting barbiturates are rapidly inactivated by hydroxylation and only a small portion is excreted unchanged in the urine. The very short acting barbiturates are mainly used for producing anesthesia or controlling seizures.

Animal Toxicology

Clinical Effects

    11.1.13) OTHER
    A) OTHER
    1) Shallow respiration, incoordination, lethargy, coma, loss of reflexes, and dilated pupils.

Treatment

    11.2.1) SUMMARY
    A) GENERAL TREATMENT
    1) SUMMARY
    a) Begin treatment immediately.
    b) Keep animal warm and do not handle unnecessarily.
    c) Remove the patient and other animals from the source of contamination or remove dietary sources.
    2) Treatment should always be done on the advice and with the consultation of a veterinarian.
    3) Additional information regarding treatment of poisoned animals may be obtained from a Veterinary Toxicologist or the National Animal Poison Control Center.
    4) ASPCA ANIMAL POISON CONTROL CENTER
    a) ASPCA Animal Poison Control Center, 1717 S Philo Road, Suite 36 Urbana, IL 61802
    b) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
    c) Contact information: (888) 426-4435 (hotline) or www.aspca.org (A fee may apply. Please inquire with the poison center). The agency will make follow-up calls as needed in critical cases at no extra charge.
    5) SMALL ANIMALS: Due to lack of reports of large animal intoxication with this substance, the following sections address small animals (dogs and cats) only.
    6) In the case of a poisoning involving large animals, consult a veterinary poison control center.
    11.2.2) LIFE SUPPORT
    A) GENERAL
    1) MAINTAIN VITAL FUNCTIONS: Secure airway, supply oxygen, and begin supportive fluid therapy if necessary.
    11.2.4) DECONTAMINATION
    A) GASTRIC DECONTAMINATION
    1) GENERAL TREATMENT
    a) EMESIS/GASTRIC LAVAGE -
    1) Induce emesis only within 30 minutes of ingestion and with extreme caution. CNS depression may occur before emesis is completed.
    2) CAUTION: Carefully examine patients with chemical exposure before inducing emesis. If signs of oral, pharyngeal, or esophageal irritation, a depressed gag reflex, or central nervous system excitation or depression are present, EMESIS SHOULD NOT BE INDUCED.
    3) HORSES OR CATTLE: DO NOT attempt to induce emesis in ruminants (cattle) or equids (horses).
    4) DOGS AND CATS
    a) IPECAC: If within 2 hours of exposure: induce emesis with 1 to 2 milliliters/kilogram syrup of ipecac per os.
    b) APOMORPHINE: Dogs may vomit more readily with 1 tablet (6 milligrams) apomorphine diluted in 3 to 5 milliliters water and instilled into the conjunctival sac or per os.
    1) Dogs may also be given apomorphine intravenously at 40 micrograms/kilogram, although this route may not be as effective.
    5) LAVAGE: In the absence of a gag reflex or if vomiting cannot be induced, place a cuffed endotracheal tube and begin gastric lavage.
    a) Pass large bore stomach tube and instill 5 to 10 milliliters/kilogram water or lavage solution, then aspirate. Repeat 10 times.
    b) ACTIVATED CHARCOAL/CATHARTIC -
    1) ACTIVATED CHARCOAL: Administer activated charcoal. Dose: 2 grams/kilogram per os or via stomach tube. Avoid aspiration by proper restraint, careful technique, and if necessary tracheal intubation.
    2) CATHARTIC: Administer a dose of a saline or sorbitol cathartic such as magnesium or sodium sulfate (sodium sulfate dose is 1 gram/kilogram). If access to these agents is limited, give 5 to 15 milliliters magnesium oxide (Milk of Magnesia) per os for dilution.
    11.2.5) TREATMENT
    A) GENERAL TREATMENT
    1) FLUIDS -
    a) Begin electrolyte and fluid therapy with isotonic solutions as needed at maintenance doses (66 milliliters solution/kilogram body weight/day intravenously) or, in hypotensive patients, at high doses (up to shock dose 60 milliliters/kilogram/hour). Monitor for urine production and pulmonary edema.
    b) Plasma administration intravenously may aid in decreasing the effective dose of the short-acting barbiturate types which are highly protein bound (Haddad & Winchester, 1983).
    2) DOXAPRAM -
    a) May be used to stimulate the respiratory and cardiovascular systems at a rate of 5.5 to 11 mg/kg slowly intravenously for dogs and cats.
    1) In neonates it can be given subcutaneously or sublingually at a total dose of 1 to 5 mg in pups and 1 to 2 mg in kittens. This also may be given slowly in the umbilical vein in pups.
    2) When stimulants are used, including doxapram, it is essential to monitor the animal closely to avoid the effects of rebound depression and possible respiratory arrest (Booth & McDonald, 1988).
    3) MONITORING -
    a) Symptomatic patients must be monitored continuously. Refer to an emergency hospital or critical care clinic for 24 hour monitoring.

Continuing Care

    11.4.1) SUMMARY
    11.4.1.2) DECONTAMINATION/TREATMENT
    A) GENERAL TREATMENT
    1) SUMMARY
    a) Begin treatment immediately.
    b) Keep animal warm and do not handle unnecessarily.
    c) Remove the patient and other animals from the source of contamination or remove dietary sources.
    2) Treatment should always be done on the advice and with the consultation of a veterinarian.
    3) Additional information regarding treatment of poisoned animals may be obtained from a Veterinary Toxicologist or the National Animal Poison Control Center.
    4) ASPCA ANIMAL POISON CONTROL CENTER
    a) ASPCA Animal Poison Control Center, 1717 S Philo Road, Suite 36 Urbana, IL 61802
    b) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
    c) Contact information: (888) 426-4435 (hotline) or www.aspca.org (A fee may apply. Please inquire with the poison center). The agency will make follow-up calls as needed in critical cases at no extra charge.
    5) SMALL ANIMALS: Due to lack of reports of large animal intoxication with this substance, the following sections address small animals (dogs and cats) only.
    6) In the case of a poisoning involving large animals, consult a veterinary poison control center.
    11.4.2) DECONTAMINATION
    11.4.2.2) GASTRIC DECONTAMINATION
    A) GASTRIC DECONTAMINATION
    1) GENERAL TREATMENT
    a) EMESIS/GASTRIC LAVAGE -
    1) Induce emesis only within 30 minutes of ingestion and with extreme caution. CNS depression may occur before emesis is completed.
    2) CAUTION: Carefully examine patients with chemical exposure before inducing emesis. If signs of oral, pharyngeal, or esophageal irritation, a depressed gag reflex, or central nervous system excitation or depression are present, EMESIS SHOULD NOT BE INDUCED.
    3) HORSES OR CATTLE: DO NOT attempt to induce emesis in ruminants (cattle) or equids (horses).
    4) DOGS AND CATS
    a) IPECAC: If within 2 hours of exposure: induce emesis with 1 to 2 milliliters/kilogram syrup of ipecac per os.
    b) APOMORPHINE: Dogs may vomit more readily with 1 tablet (6 milligrams) apomorphine diluted in 3 to 5 milliliters water and instilled into the conjunctival sac or per os.
    1) Dogs may also be given apomorphine intravenously at 40 micrograms/kilogram, although this route may not be as effective.
    5) LAVAGE: In the absence of a gag reflex or if vomiting cannot be induced, place a cuffed endotracheal tube and begin gastric lavage.
    a) Pass large bore stomach tube and instill 5 to 10 milliliters/kilogram water or lavage solution, then aspirate. Repeat 10 times.
    b) ACTIVATED CHARCOAL/CATHARTIC -
    1) ACTIVATED CHARCOAL: Administer activated charcoal. Dose: 2 grams/kilogram per os or via stomach tube. Avoid aspiration by proper restraint, careful technique, and if necessary tracheal intubation.
    2) CATHARTIC: Administer a dose of a saline or sorbitol cathartic such as magnesium or sodium sulfate (sodium sulfate dose is 1 gram/kilogram). If access to these agents is limited, give 5 to 15 milliliters magnesium oxide (Milk of Magnesia) per os for dilution.

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