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BARIUM SULFATE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Barium sulfate is a radiopaque agent. It is insoluble and not well absorbed.

Specific Substances

    1) Barii Sulfas
    2) Barii Sulphas
    3) Barium Sulfate
    4) Barium Sulfuricum
    5) Baryum (Sulfate de)
    6) Molecular Formula: BaSO4
    1.2.1) MOLECULAR FORMULA
    1) BaSO4
    2) O4-S.Ba
    3) Ba.H2-O4-S

Available Forms Sources

    A) FORMS
    1) Barium sulfate is a white or yellowish, odorless, tasteless, fine, heavy orthorhombic powder or crystalline solid (Budavari, 2001; HSDB, 2003; IPCS, 2001). Barite, the mineral from which barium sulfate is produced, exists as a moderately soft, crystalline, white opaque or transparent mineral (IPCS, 2001).
    a) Impurities of iron(III) oxide, aluminum oxide, silica, and strontium sulfate may occur in barium sulfate (IPCS, 2001).
    2) The barium sulfate used in drilling muds is ground to an average particle diameter of 44 mcm, with no more than 30% of particles smaller than 6 mcm in diameter (IPCS, 2001).
    3) Barium sulfate is found in the following grades (Lewis, 2001):
    1) technical
    2) dry
    3) pulp
    4) bleached
    5) ground
    6) floated
    7) natural
    8) CP
    9) USP
    10) X-ray
    B) SOURCES
    1) Barium sulfate occurs in nature as the mineral barite ("heavy spar" or "barytes"); barite can be comprised of as much as 80 - 90% barium sulfate (Budavari, 2001; Harbison, 1998; IPCS, 2001; Lewis, 2001).
    2) It is produced from high-grade (>75%) barite ore, generally found in association with shale and granite. The ore is crushed, then beneficiated by froth floatation or jigging, and dried (ACGIH, 2001a; ATSDR, 1992).
    3) It can be derived by treating a solution of a barium salt with sodium sulfate (e.g., barium sulfide + sodium sulfate), or by treating barium chloride or barium carbonate with sulfuric acid (Ashford, 2001; HSDB, 2003).
    4) "Blanc fixe" is produced by mixing an aqueous solution of barium sulfide and sodium sulfate in order to precipitate uniform particles of pigmentary fineness (HSDB, 2003).
    5) It occurs as a by-product of hydrogen peroxide manufacturing (HSDB, 2003).
    C) USES
    1) MEDICAL
    a) Barium sulfate is used as a contrast medium for radiographic examination of the gastrointestinal tract involving single- or double-contrast techniques or computed tomography. It is also used as a contrast medium in brachography where it is introduced into the bronchial tract, and it used in X-ray examination of the urinary system (S Sweetman , 2001; ACGIH, 2001a).
    2) INDUSTRIAL
    a) The majority of barite (crude barium sulfate) is employed for lubrication purposes as a high-density mud weighting compound in oil and gas well drilling(Pohanish, 2002; ATSDR, 1992; ATSDR, 1995).
    b) Barium sulfate is also used in the manufacture of cellophane, artifical ivory, and photographic papers; as a water-color pigment in wallpaper or colored paper; in heavy concrete for radiation shielding; in battery plate expanders; in brake linings; in some sealants and adhesives; as a filler for plastics, rubber, polymeric fibers and resins, papers and inks; as a weighting substance in some golf balls; as a pigment extender in paints; as a delustrant for textiles; and as a hardening agent for cement (Budavari, 2001; HSDB, 2003; IPCS, 2001; Lewis, 2001).
    1) In its chemically treated form, "blanc fixe," barium sulfate is used as a pigment in high-quality paints and in paper and glass making (ACGIH, 2001a; ATSDR, 1992; Pohanish, 2002).
    a) Lithopone, a white powder containing approximately 70% barium sulfate, is used as a pigment in white paints. However, lithopone may be phased out of commercial use as the U.S. markets increasingly turn to titanium dioxide for use as a white pigment (ATSDR, 1992; Harbison, 1998; HSDB, 2003).

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: Barium sulfate is used as an oral or rectal contrast agent in radiologic studies. In industry it is used as a lubricant, as a pigment in paints, and in manufacturing of cellophane, photographic papers, brake linings and adhesives.
    B) PHARMACOLOGY: Barium is used in radiologic procedures because it is radiopaque.
    C) EPIDEMIOLOGY: Overdose is very rare, exposure rarely causes significant adverse effects.
    D) WITH THERAPEUTIC USE
    1) Oral or rectal barium sulfate administration may cause constipation, impaction, obstruction, cramping, and diarrhea. Appendicitis, bowel perforation, peritonitis and proctitis have been reported rarely after oral or rectal barium sulfate use in radiologic procedures.
    2) ECG abnormalities have been reported. Aspiration of barium sulfate may cause pneumonitis, granuloma formation, severe dyspnea, and hypoxemia. Dyspnea and hypoxemia usually resolve quickly with supportive care.
    3) Venous intravasation has been reported following the use of barium enemas, and may be complicated by barium pulmonary emboli.
    E) WITH POISONING/EXPOSURE
    1) Barium sulfate is almost insoluble and lacks the severe toxicity characteristic of the barium ion.
    0.2.20) REPRODUCTIVE
    A) Although barium sulfate is not systemically absorbed or metabolized by the body, prenatal radiation exposure has been shown to cause fetal harm. During pregnancy, perform only those radiographic procedures that are deemed essential to the mother's health. Breastfeeding mothers may use barium sulfate products without adversely affecting their infants.
    0.2.21) CARCINOGENICITY
    A) Occupational exposure via inhalation has resulted in baritosis a benign pneumoconiosis. At the time of this review, carcinogenicity has not been reported.

Laboratory Monitoring

    A) No specific laboratory studies are needed in most patients.
    B) Persons who are exposed to barium sulfate dust or who aspirate barium may be monitored with periodic chest X-rays and pulmonary function tests.
    C) Barium can be measured in urine and blood, but these studies are not useful for guiding clinical management.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Significant toxicity is not expected after ingestion. Treat mild allergic reaction with antihistamines and corticosteroids. More severe reactions may require inhaled beta agonists and epinephrine.
    B) DECONTAMINATION
    1) Barium sulfate is not absorbed, GI decontamination is not necessary.
    C) ENHANCED ELIMINATION
    1) There is no role for hemodialysis or hemoperfusion.
    D) PITFALLS
    1) Toxicity is not expected after ingestion, overtreatment is the greatest risk. Barium should not be used as a contrast agent if perforation of an esophagus, stomach or bowel is suspected of if aspiration is a serious risk.
    E) PHARMACOKINETICS
    1) Barium sulfate is not absorbed orally.
    F) DIFFERENTIAL DIAGNOSIS
    1) Other non-toxic ingestion
    G) PATIENT DISPOSITION
    1) HOME CRITERIA: Patients with inadvertent ingestions can be managed at home. Patients with deliberate ingestions should be sent to a medical facility for psychiatric evaluation.
    2) ADMISSION CRITERIA: Patients with significant aspiration, intravenous injection or peritoneal contamination with barium should be admitted.
    3) CONSULT CRITERIA: Consult a surgeon for any patient with suspected barium leakage into the peritoneum. Consult a pulmonologist for suspected barium aspiration.
    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.
    B) BRONCHOSCOPY
    1) Patients with severe aspiration may benefit from bronchoscopy.
    0.4.4) EYE EXPOSURE
    A) Irrigate exposed eyes with water

Range Of Toxicity

    A) A toxic dose has not been established. Barium sulfate is almost insoluble; systemic toxicity has not been reported after ingestion. Aspiration and intravenous administration may be fatal.

Clinical Effects

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) ACUTE ALLERGIC REACTION
    1) WITH THERAPEUTIC USE
    a) Anaphylactoid reaction (wheezing, tightness in chest, or troubled breathing) may occur following the use of barium sulfate (USPDI , 2001).
    1) CASE REPORT: A patient developed anaphylactic shock after being given a barium sulfate enema (Al-Mudallal et al, 1990).
    b) A survey involving 167 members of a radiologists professional society, the FDA, 3 main suppliers of barium products, and a review of the American medical literature was conducted regarding barium hypersensitivity reactions. A total of 106 hypersensitivity reactions were identified in which 61% involved cutaneous reactions, 8% respiratory reactions, 21% were unclassified, and 8% of patients experienced loss of consciousness (Janower, 1986).
    c) In addition, allergic-like reactions may due to additives in the barium sulfate suspension, rectal lubricants, the latex inflatable cuff on some enema tips, or other medications given at the time of the procedure (e.g., glucagon, anticholinergic agents) (USPDI , 2001).

Reproductive

    3.20.1) SUMMARY
    A) Although barium sulfate is not systemically absorbed or metabolized by the body, prenatal radiation exposure has been shown to cause fetal harm. During pregnancy, perform only those radiographic procedures that are deemed essential to the mother's health. Breastfeeding mothers may use barium sulfate products without adversely affecting their infants.
    3.20.2) TERATOGENICITY
    A) FETAL HARM
    1) Although barium sulfate is not systemically absorbed or metabolized by the body, prenatal radiation exposure has been shown to cause fetal harm (Prod Info E-Z-HD oral suspension, 2016; Prod Info E-Z-CAT DRY(R) oral powder for suspension, 2014; Prod Info E-Z-DISK(TM) oral tablets, 2014; Prod Info E-Z-DOSE(TM) WITH LIQUID POLIBAR PLUS(R) rectal suspension, 2011; Prod Info E-Z-PASTE(R) oral cream, 2014).
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF EFFECT
    1) Since barium sulfate is not systemically absorbed or metabolized, its use is not expected to adversely affect pregnancy (Prod Info E-Z-HD oral suspension, 2016).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) Breastfeeding mothers may use barium sulfate products without adversely affecting their infants (Prod Info E-Z-HD oral suspension, 2016; Prod Info E-Z-CAT DRY(R) oral powder for suspension, 2014; Prod Info E-Z-DISK(TM) oral tablets, 2014; Prod Info E-Z-DOSE(TM) WITH LIQUID POLIBAR PLUS(R) rectal suspension, 2011; Prod Info E-Z-PASTE(R) oral cream, 2014).
    3.20.5) FERTILITY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of barium sulfate exposure on human fertility.
    B) ANIMAL STUDIES
    1) No animal studies have evaluated the potential effects of barium sulfate exposure on fertility (Prod Info E-Z-HD oral suspension, 2016).

Summary Of Exposure

    A) USES: Barium sulfate is used as an oral or rectal contrast agent in radiologic studies. In industry it is used as a lubricant, as a pigment in paints, and in manufacturing of cellophane, photographic papers, brake linings and adhesives.
    B) PHARMACOLOGY: Barium is used in radiologic procedures because it is radiopaque.
    C) EPIDEMIOLOGY: Overdose is very rare, exposure rarely causes significant adverse effects.
    D) WITH THERAPEUTIC USE
    1) Oral or rectal barium sulfate administration may cause constipation, impaction, obstruction, cramping, and diarrhea. Appendicitis, bowel perforation, peritonitis and proctitis have been reported rarely after oral or rectal barium sulfate use in radiologic procedures.
    2) ECG abnormalities have been reported. Aspiration of barium sulfate may cause pneumonitis, granuloma formation, severe dyspnea, and hypoxemia. Dyspnea and hypoxemia usually resolve quickly with supportive care.
    3) Venous intravasation has been reported following the use of barium enemas, and may be complicated by barium pulmonary emboli.
    E) WITH POISONING/EXPOSURE
    1) Barium sulfate is almost insoluble and lacks the severe toxicity characteristic of the barium ion.

Heent

    3.4.5) NOSE
    A) WITH THERAPEUTIC USE
    1) ALLERGIC RHINITIS: Following a dose of barium sulfate suspension during a barium study of the gastrointestinal tract, a patient exhibited allergic rhinitis (sneezing, nasal congestion, and rhinorrhea) which reoccurred on rechallenge (Shaffer et al, 1988).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) CONDUCTION DISORDER OF THE HEART
    1) WITH THERAPEUTIC USE
    a) ECG changes have been reported during the use of barium sulfate enema (S Sweetman , 2001).
    b) CASE REPORT: Dysrhythmias ranging from ventricular fibrillation, bradycardia, and asystole developed in a 67-year-old man following venous intravasation of barium sulfate during roentgenography of the colon (Tsoutsanis, 1981).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) DYSPNEA
    1) WITH THERAPEUTIC USE
    a) CASE REPORTS: Severe dyspnea and hypoxemia developed in 2 patients after they aspirated significant amounts of barium sulfate while undergoing radiographic procedures (Tamm & Kortsik, 1999). Both patients recovered rapidly with return to normal pulmonary function despite persistent evidence of barium in the lungs on chest radiograph.
    B) PULMONARY EMBOLISM
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: Intravasation of barium sulfate occurred during roentgenography of the colon in a 67-year-old man. Various cardiovascular effects including dysrhythmias developed. Over a few days, the patient's condition deteriorated. The patient subsequently died from respiratory failure. On postmortem examination, barium pulmonary emboli were identified (Tsoutsanis, 1981).
    C) PNEUMONITIS
    1) WITH THERAPEUTIC USE
    a) Aspiration of barium sulfate may result in severe pneumonitis and respiratory failure (S Sweetman , 2001; Penington, 1993).
    b) CASE REPORT: A 77-year-old man with a 2-month history of dysphagia and cough presented to the hospital where a esophagography with barium sulfate was performed. Within minutes, the patient developed respiratory failure. The esophagography films indicated a tracheoesophageal fistula with radiopaque material inside the respiratory tract, indicating barium aspiration. Despite immediate orotracheal intubation and bronchoscopy, the patient's condition deteriorated with the development of ARDS and cardiac arrest. Cardiopulmonary resuscitation was unsuccessful (Rodriguez-Gutierrez et al, 2014).
    D) BARITOSIS
    1) WITH POISONING/EXPOSURE
    a) Inhalation of fine dusts may produce harmless nodular granules in lungs (Baritosis). This is reversible and does not affect pulmonary function (HSDB , 2001; S Sweetman , 2001).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) DRUG-INDUCED GASTROINTESTINAL DISTURBANCE
    1) WITH THERAPEUTIC USE
    a) Constipation, impaction, obstruction, diarrhea, cramping, and barium granuloma have been reported following the use of barium sulfate (S Sweetman , 2001).
    B) APPENDICITIS
    1) WITH THERAPEUTIC USE
    a) The development of acute appendicitis with perforation, possibly due to retained barium sulfate fecolith, has been reported after barium sulfate enema (Sisley & Wagner, 1982).
    C) PERFORATION OF INTESTINE
    1) WITH THERAPEUTIC USE
    a) Bowel perforation occurs rarely after oral or rectal administration of barium sulfate for radiographic studies, but it may cause peritonitis, adhesions, granulomas, and a high mortality rate (S Sweetman , 2001).
    D) PERITONITIS
    1) WITH THERAPEUTIC USE
    a) Following the use of barium enema, acute peritonitis has rarely been reported (Yamamura et al, 1985; (Gnanaprakasam et al, 1981). In one case, the barium was aspirated as much as possible, but systemic cleansing of the peritoneal cavity with a urokinase solution was required to successfully remove barium in an 80-year-old patient who had peritonitis resulting from a perforated sigmoid colon (Yamamura et al, 1985).
    E) PROCTITIS
    1) WITH THERAPEUTIC USE
    a) Necrotizing proctitis was diagnosed 2 weeks following a barium enema examination in a 70-year-old woman. A sigmoidostomy was performed and the patient initially recovered but was readmitted 6 months later at which time the rectal lumen was stenotic and stiff and barium was found on repeated biopsies (Lazarovitch et al, 1980).
    F) ANGIOEDEMA
    1) WITH THERAPEUTIC USE
    a) An allergic reaction during a barium sulfate study of the gastrointestinal tract resulted in angioedema of the stomach and small bowel (Shaffer et al, 1988).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) DISSEMINATED INTRAVASCULAR COAGULATION
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: Following venous intravasation of a barium sulfate enema, disseminated intravascular coagulation developed in an elderly patient (JEF Reynolds , 1990).
    B) LACK OF EFFECT
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: Venous intravasation occurred in an 86-year-old patient following a barium enema. The patient had an uneventful recovery, which the investigators theorized was due to the minimal amount of barium introduced (maximum 5 mL) (Archer & Freeman, 1981).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS7727-43-7 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed
    3.21.2) SUMMARY/HUMAN
    A) Occupational exposure via inhalation has resulted in baritosis a benign pneumoconiosis. At the time of this review, carcinogenicity has not been reported.
    3.21.3) HUMAN STUDIES
    A) BENIGN PNEUMOCONIOSIS
    1) Occupational exposure to barium sulfate via inhalation has lead to baritosis a benign pneumoconiosis. This condition has developed in the mining grinding and bagging on barite, the nodules are usually less than 3 mm in size (HSDB, 2003).
    3.21.4) ANIMAL STUDIES
    A) CARCINOMA
    1) In animal studies, bronchogenic carcinoma (squamous cell type) has been reported following intratracheal injections with radioactive particles of (35)S-barium sulfate (HSDB , 2001).
    2) Barium sulfate was an equivocal tumorigenic agent when implanted intrapleurally in rats (RTECS , 2001).

Genotoxicity

    A) At the time of this review, no genetic information was available.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No specific laboratory studies are needed in most patients.
    B) Persons who are exposed to barium sulfate dust or who aspirate barium may be monitored with periodic chest X-rays and pulmonary function tests.
    C) Barium can be measured in urine and blood, but these studies are not useful for guiding clinical management.

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 aspiration, intravenous injection or peritoneal contamination with barium should be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Patients with inadvertent ingestions can be managed at home. Patients with deliberate ingestions should be sent to a medical facility for psychiatric evaluation.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a surgeon for any patient with suspected barium leakage into the peritoneum. Consult a pulmonologist for suspected barium aspiration.

Monitoring

    A) No specific laboratory studies are needed in most patients.
    B) Persons who are exposed to barium sulfate dust or who aspirate barium may be monitored with periodic chest X-rays and pulmonary function tests.
    C) Barium can be measured in urine and blood, but these studies are not useful for guiding clinical management.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) Minimal toxicity is expected after acute ingestion. Gastrointestinal decontamination is generally not necessary.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) Significant toxicity is not anticipated after ingestion. Treatment is symptomatic and supportive. Gastrointestinal decontamination is not generally necessary.
    6.5.3) TREATMENT
    A) SUPPORT
    1) In case of barium sulfate overdose ingestion, treatment is symptomatic and supportive. Significant toxicity is not expected after ingestion unless the patient develops an anaphylactoid reaction. Barium can cause significant toxicity after aspiration, intravasation or leakage into the peritoneum from a perforated viscus.
    B) MONITORING OF PATIENT
    1) No specific laboratory studies are needed in most patients.
    2) Persons who are exposed to barium sulfate dust or who aspirate barium may be monitored with periodic chest X-rays and pulmonary function tests.
    3) Barium can be measured in urine and blood, but these studies are not useful for guiding clinical management.
    C) ACUTE ALLERGIC REACTION
    1) SUMMARY
    a) Mild to moderate allergic reactions may be treated with antihistamines with or without inhaled beta adrenergic agonists, corticosteroids or epinephrine. Treatment of severe anaphylaxis also includes oxygen supplementation, aggressive airway management, epinephrine, ECG monitoring, and IV fluids.
    2) BRONCHOSPASM
    a) ALBUTEROL
    1) ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007). CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 mg/kg (up to 10 mg) every 1 to 4 hours as needed, or 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    3) CORTICOSTEROIDS
    a) Consider systemic corticosteroids in patients with significant bronchospasm.
    b) PREDNISONE: ADULT: 40 to 80 milligrams/day. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 to 2 divided doses divided twice daily (National Heart,Lung,and Blood Institute, 2007).
    4) MILD CASES
    a) DIPHENHYDRAMINE
    1) SUMMARY: Oral diphenhydramine, as well as other H1 antihistamines can be used as indicated (Lieberman et al, 2010).
    2) ADULT: 50 milligrams orally, or 10 to 50 mg intravenously at a rate not to exceed 25 mg/min or may be given by deep intramuscular injection. A total of 100 mg may be administered if needed. Maximum daily dosage is 400 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    3) CHILD: 5 mg/kg/24 hours or 150 mg/m(2)/24 hours. Divided into 4 doses, administered intravenously at a rate not exceeding 25 mg/min or by deep intramuscular injection. Maximum daily dosage is 300 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    5) MODERATE CASES
    a) EPINEPHRINE: INJECTABLE SOLUTION: It should be administered early in patients by IM injection. Using a 1:1000 (1 mg/mL) solution of epinephrine. Initial Dose: 0.01 mg/kg intramuscularly with a maximum dose of 0.5 mg in adults and 0.3 mg in children. The dose may be repeated every 5 to 15 minutes, if no clinical improvement. Most patients respond to 1 or 2 doses (Nowak & Macias, 2014).
    6) SEVERE CASES
    a) EPINEPHRINE
    1) INTRAVENOUS BOLUS: ADULT: 1 mg intravenously as a 1:10,000 (0.1 mg/mL) solution; CHILD: 0.01 mL/kg intravenously to a maximum single dose of 1 mg given as a 1:10,000 (0.1 mg/mL) solution. It can be repeated every 3 to 5 minutes as needed. The dose can also be given by the intraosseous route if IV access cannot be established (Lieberman et al, 2015). ALTERNATIVE ROUTE: ENDOTRACHEAL ADMINISTRATION: If IV/IO access is unavailable. DOSE: ADULT: Administer 2 to 2.5 mg of 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube. CHILD: DOSE: 0.1 mg/kg to a maximum of 2.5 mg administered as a 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube (Lieberman et al, 2015).
    2) INTRAVENOUS INFUSION: Intravenous administration may be considered in patients poorly responsive to IM or SubQ epinephrine. An epinephrine infusion may be prepared by adding 1 mg (1 mL of 1:1000 (1 mg/mL) solution) to 250 mL D5W, yielding a concentration of 4 mcg/mL, and infuse this solution IV at a rate of 1 mcg/min to 10 mcg/min (maximum rate). CHILD: A dosage of 0.01 mg/kg (0.1 mL/kg of a 1:10,000 (0.1 mg/mL) solution up to 10 mcg/min (maximum dose 0.3 mg) is recommended for children (Lieberman et al, 2010). Careful titration of a continuous infusion of IV epinephrine, based on the severity of the reaction, along with a crystalloid infusion can be considered in the treatment of anaphylactic shock. It appears to be a reasonable alternative to IV boluses, if the patient is not in cardiac arrest (Vanden Hoek,TL,et al).
    7) AIRWAY MANAGEMENT
    a) OXYGEN: 5 to 10 liters/minute via high flow mask.
    b) INTUBATION: Perform early if any stridor or signs of airway obstruction.
    c) CRICOTHYROTOMY: Use if unable to intubate with complete airway obstruction (Vanden Hoek,TL,et al).
    d) BRONCHODILATORS are recommended for mild to severe bronchospasm.
    e) ALBUTEROL: ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007).
    f) ALBUTEROL: CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    8) MONITORING
    a) CARDIAC MONITOR: All complicated cases.
    b) IV ACCESS: Routine in all complicated cases.
    9) HYPOTENSION
    a) If hypotensive give 500 to 2000 milliliters crystalloid initially (20 milliliters/kilogram in children) and titrate to desired effect (stabilization of vital signs, mentation, urine output); adults may require up to 6 to 10 L/24 hours. Central venous or pulmonary artery pressure monitoring is recommended in patients with persistent hypotension.
    1) VASOPRESSORS: Should be used in refractory cases unresponsive to repeated doses of epinephrine and after vigorous intravenous crystalloid rehydration (Lieberman et al, 2010).
    2) DOPAMINE: Initial Dose: 2 to 20 micrograms/kilogram/minute intravenously; titrate to maintain systolic blood pressure greater than 90 mm Hg (Lieberman et al, 2010).
    10) H1 and H2 ANTIHISTAMINES
    a) SUMMARY: Antihistamines are second-line therapy and are used as supportive therapy and should not be used in place of epinephrine (Lieberman et al, 2010).
    1) DIPHENHYDRAMINE: ADULT: 25 to 50 milligrams via a slow intravenous infusion or IM. PEDIATRIC: 1 milligram/kilogram via slow intravenous infusion or IM up to 50 mg in children (Lieberman et al, 2010).
    b) RANITIDINE: ADULT: 1 mg/kg parenterally; CHILD: 12.5 to 50 mg parenterally. If the intravenous route is used, ranitidine should be infused over 10 to 15 minutes or diluted in 5% dextrose to a volume of 20 mL and injected over 5 minutes (Lieberman et al, 2010).
    c) Oral diphenhydramine, as well as other H1 antihistamines, can also be used as indicated (Lieberman et al, 2010).
    11) DYSRHYTHMIAS
    a) Dysrhythmias and cardiac dysfunction may occur primarily or iatrogenically as a result of pharmacologic treatment (epinephrine) (Vanden Hoek,TL,et al). Monitor and correct serum electrolytes, oxygenation and tissue perfusion. Treat with antiarrhythmic agents as indicated.
    12) OTHER THERAPIES
    a) There have been a few reports of patients with anaphylaxis, with or without cardiac arrest, that have responded to vasopressin therapy that did not respond to standard therapy. Although there are no randomized controlled trials, other alternative vasoactive therapies (ie, vasopressin, norepinephrine, methoxamine, and metaraminol) may be considered in patients in cardiac arrest secondary to anaphylaxis that do not respond to epinephrine (Vanden Hoek,TL,et al).

Inhalation Exposure

    6.7.2) TREATMENT
    A) PULMONARY ASPIRATION
    1) 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.
    2) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    3) 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.
    4) BRONCHOSPASM SUMMARY
    a) Administer beta2 adrenergic agonists. Consider use of inhaled ipratropium and systemic corticosteroids. Monitor peak expiratory flow rate, monitor for hypoxia and respiratory failure, and administer oxygen as necessary.
    5) ALBUTEROL/ADULT DOSE
    a) 2.5 to 5 milligrams diluted with 4 milliliters of 0.9% saline by nebulizer every 20 minutes for three doses. If incomplete response, administer 2.5 to 10 milligrams every 1 to 4 hours as needed OR administer 10 to 15 milligrams every hour by continuous nebulizer as needed. Consider adding ipratropium to the nebulized albuterol; DOSE: 0.5 milligram by nebulizer every 30 minutes for three doses then every 2 to 4 hours as needed, NOT administered as a single agent (National Heart,Lung,and Blood Institute, 2007).
    6) ALBUTEROL/PEDIATRIC DOSE
    a) 0.15 milligram/kilogram (minimum 2.5 milligrams) diluted with 4 milliliters of 0.9% saline by nebulizer every 20 minutes for three doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulizer as needed. Consider adding ipratropium to the nebulized albuterol; DOSE: 0.25 to 0.5 milligram by nebulizer every 20 minutes for three doses then every 2 to 4 hours as needed, NOT administered as a single agent (National Heart,Lung,and Blood Institute, 2007).
    7) ALBUTEROL/CAUTIONS
    a) The incidence of adverse effects of beta2-agonists may be increased in older patients, particularly those with pre-existing ischemic heart disease (National Asthma Education and Prevention Program, 2007). Monitor for tachycardia, tremors.
    8) CORTICOSTEROIDS
    a) Consider systemic corticosteroids in patients with significant bronchospasm. PREDNISONE: ADULT: 40 to 80 milligrams/day in 1 or 2 divided doses. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 or 2 divided doses (National Heart,Lung,and Blood Institute, 2007).
    9) Some authors have advocated bronchoscopy to remove large barium sulfate deposits in the lungs in patients who develop hypoxemia after aspiration (Tamm & Kortsik, 1999). Most patients do well with supportive care, despite persistent evidence of barium in the lung on chest radiograph.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Range Of Toxicity

Summary

    A) A toxic dose has not been established. Barium sulfate is almost insoluble; systemic toxicity has not been reported after ingestion. Aspiration and intravenous administration may be fatal.

Therapeutic Dose

    7.2.1) ADULT
    A) ORAL
    1) ESOPHAGEAL CREAM (60% w/w): 1 to 4 teaspoons, as required (Prod Info E-Z-PASTE(R) oral cream, 2014)
    2) POWDER SUSPENSION
    a) ABDOMEN STUDIES: 300 mL 30 minutes before scan and 150 mL immediately before scan, or as directed by physician (Prod Info E-Z-CAT DRY(R) oral powder for suspension, 2014)
    b) ABDOMEN/PELVIS STUDIES: 450 mL 90 minutes before scan, another 300 mL 30 minutes before scan, and 150 mL immediately before scan, or as directed by physician (Prod Info E-Z-CAT DRY(R) oral powder for suspension, 2014)
    c) ESOPHAGUS, STOMACH, AND DUODENUM STUDIES: 65 to 135 mL (155 to 321 g barium sulfate) orally; use volume closer to 65 mL for esophagus and up to 135 mL for entire upper gastrointestinal tract (Prod Info E-Z-HD oral suspension, 2016)
    3) SUSPENSION LIQUID AND SMOOTHIE (12 years or older): 450 to 900 mL (9 to 18 g barium sulfate) orally, prior to scan (Prod Info READI-CAT(R) 2 oral suspension, 2016; Prod Info READI-CAT(R) 2 SMOOTHIE oral suspension, 2016)
    4) TABLET: One 700 mg tablet swallowed whole with 1 or 2 swallows of water immediately before fluoroscopy (Prod Info E-Z-DISK(TM) oral tablets, 2014)
    B) RECTAL
    1) COLON STUDIES: 500 mL to 1500 mL, depending on the patient's body habits and radiographic procedures requested (Prod Info E-Z-DOSE(TM) WITH LIQUID POLIBAR PLUS(R) rectal suspension, 2011)
    7.2.2) PEDIATRIC
    A) ORAL
    1) POWDER SUSPENSION
    a) ESOPHAGUS, STOMACH, AND DUODENUM STUDIES (12 years or older): 65 to 135 mL (155 to 321 g barium sulfate) orally; use volume closer to 65 mL for esophagus and up to 135 mL for entire upper gastrointestinal tract (Prod Info E-Z-HD oral suspension, 2016)
    2) SUSPENSION LIQUID AND SMOOTHIE
    a) ABDOMEN STUDIES (12 years or older): 450 to 900 mL (9 to 18 g barium sulfate) orally, prior to scan (Prod Info READI-CAT(R) 2 oral suspension, 2016; Prod Info READI-CAT(R) 2 SMOOTHIE oral suspension, 2016)
    b) ABDOMEN STUDIES (younger than 12 years): Dose should be based on relative GI volume and administered orally prior to scan (Prod Info READI-CAT(R) 2 oral suspension, 2016; Prod Info READI-CAT(R) 2 SMOOTHIE oral suspension, 2016).

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) The minimum lethal human dose to this agent has not been delineated.
    B) CASE REPORTS
    1) Ingestion of radioactive barium sulfate used in gastrointestinal imaging caused fatal acute hypersensitivity reactions to in two patients (amount not specified) (IPCS, 1990).
    2) Accidental inhalation of barium sulfate caused fatal acute inflammation of the bronchi and peripheral airways in two cases (concentration not specified) (IPCS, 1990).
    3) An adult female died following acute intraversion of barium sulfate during a barium sulfate enema. Cardiorespiratory failure was thought to have been caused by direct entry of the barium sulfate into the blood stream (amount not specified) (ATSDR, 1992).

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) No specific maximum tolerated exposure amount has been determined.
    2) The paucity of case reports on its systemic toxicity, despite routine oral administration of 450 grams barium sulfate as an x-ray medium, indicate that ingestion of barium sulfate is not toxic (IPCS, 2001).
    B) ANIMAL DATA
    1) Barium sulfate exposure at 40 mg/m(3) (particle size 1-2 mcm) for 5 hours/day, 5 days/week for up to 2 months caused minor histopathological changes in the lungs of rats, with no evidence of fibrogenic potential. Singular exposure caused thickening of the alveolar septa, loss of ciliated epithelial cells, and the formation of multicellular epithelium. The alveolar septa returned to normal after14 days of treatment, though changes in the bronchiolar epithelium were noted after a 28 day recovery period (IPCS, 2001).
    2) Intratracheal administration of up to 0.6 mL/kg "Ba147," a preparation containing 85% barium sulfate, to rabbits did not affect pulmonary ventilation, levels of blood gases, or lung weights. Twenty-eight of the 36 animals tested exhibited symptoms of bronchopneumonia, bronchitis, or bronchiolitis within the first week after dosing (EPA, 1998).
    3) Instillation of barium sulfate in the respiratory tract of animals resulted in granuloma formation and inflammatory responses, as would be expected with exposure to high levels of any low-solubility dust (IPCS, 2001).

Workplace Standards

    A) ACGIH TLV Values for CAS7727-43-7 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.
    a) Adopted Value
    1) Barium sulfate
    a) TLV:
    1) TLV-TWA: 10 mg/m(3)
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: Not Listed
    2) Codes: Not Listed
    3) Definitions: Not Listed
    c) TLV Basis - Critical Effect(s): Pneumoconiosis
    d) Molecular Weight: 233.43
    1) For gases and vapors, to convert the TLV from ppm to mg/m(3):
    a) [(TLV in ppm)(gram molecular weight of substance)]/24.45
    2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:
    a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance
    e) Additional information:
    b) Under Study
    1) Barium sulfate
    a) TLV:
    1) TLV-TWA:
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: Not Listed
    2) Codes: Not Listed
    3) Definitions: Not Listed
    c) TLV Basis - Critical Effect(s):
    d) Molecular Weight:
    1) For gases and vapors, to convert the TLV from ppm to mg/m(3):
    a) [(TLV in ppm)(gram molecular weight of substance)]/24.45
    2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:
    a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance
    e) Additional information:

    B) NIOSH REL and IDLH Values for CAS7727-43-7 (National Institute for Occupational Safety and Health, 2007):
    1) Listed as: Barium sulfate
    2) REL:
    a) TWA: 10 mg/m(3) (total) 5 mg/m(3) (resp)
    b) STEL:
    c) Ceiling:
    d) Carcinogen Listing: (Not Listed) Not Listed
    e) Skin Designation: Not Listed
    f) Note(s):
    3) IDLH: Not Listed

    C) Carcinogenicity Ratings for CAS7727-43-7 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed ; Listed as: Barium sulfate
    2) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed ; Listed as: Barium sulfate
    3) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    4) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    5) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed ; Listed as: Barium sulfate
    6) MAK (DFG, 2002): Not Listed
    7) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS7727-43-7 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Listed as: Barium sulfate (Total dust)
    2) Table Z-1 for Barium sulfate (Total dust):
    a) 8-hour TWA:
    1) ppm:
    a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.
    2) mg/m3: 15
    a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.
    3) Ceiling Value:
    4) Skin Designation: No
    5) Notation(s): Not Listed
    3) Listed as: Barium sulfate (Respirable fraction)
    4) Table Z-1 for Barium sulfate (Respirable fraction):
    a) 8-hour TWA:
    1) ppm:
    a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.
    2) mg/m3: 5
    a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.
    3) Ceiling Value:
    4) Skin Designation: No
    5) Notation(s): Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES

Physicochemical

Physical Characteristics

    A) Barium sulfate is a white or yellowish, odorless, tasteless fine, heavy powder or polymorphous crystalline solid. It is practically insoluble in water, but is soluble in hot concentrated sulfuric acid (ACGIH, 2001; Budavari, 2001; HSDB, 2003; Lewis, 2001).
    B) Barium sulfate exists as white, orthorhombic crystals (Lide, 1996).

Ph

    A) 5% barium sulfate suspension in water is neutral (HSDB, 2003)

Molecular Weight

    A) 233.39

References

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