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SODIUM BICARBONATE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Sodium bicarbonate is used therapeutically as an antacid and a urinary and systemic alkalinizer.

Specific Substances

    1) Baking Soda
    2) Sal de Vichy
    3) Sodium Acid Carbonate
    4) Sodium Hydrocarbonate
    5) Sodium Hydrogen Carbonate
    6) CAS 144-55-8
    1.2.1) MOLECULAR FORMULA
    1) C-H-O3.Na NaHCO3

Available Forms Sources

    A) FORMS
    1) Sodium bicarbonate is the main (if not only) constituent of most baking sodas, and may be an ingredient of folk remedies containing turpentine, castor oil, lemon and sugar.
    2) Poisonings have occurred in infants where sodium bicarbonate was inadvertently substituted for powdered infant formula (DelBeccaro & (Robertson, 1988) Robertson, 1988).
    B) USES
    1) Sodium bicarbonate is also added to mouthwashes and dentifrices to prevent dental caries. It is employed as an additive in meat processing and used to clean and neutralize acidity in vegetables (HSDB , 2002).
    2) Sodium bicarbonate may be an ingredient of folk remedies containing turpentine, castor oil, lemon and sugar.

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: Sodium bicarbonate is used to treat metabolic acidosis, hyperkalemia, to treat QRS widening and dysrhythmias resulting from drugs that cause sodium channel blockade, to prevent contrast-induce nephropathy, and to alkalinize the urine. It is also present in antacids, mouthwash and baking soda. It is also an additive in meat processing and used to clean and neutralize acidity in vegetables.
    B) PHARMACOLOGY: Sodium bicarbonate dissociates to provide bicarbonate ions. Bicarbonate neutralizes hydrogen ion concentration and raises blood and urinary pH. Dissociated sodium ions help to overcome sodium channel blockade from certain sodium channel blocking drugs.
    C) TOXICOLOGY: Toxic effects from sodium bicarbonate are secondary to the sodium and bicarbonate ions which causes hypernatremia, alkalosis, and other secondary effects.
    D) EPIDEMIOLOGY: Sodium bicarbonate is extremely common in the environment and potential exposures are very common but rarely serious. Indeed, it is given as a treatment for many seriously ill patients. However, fatalities, though very rare, can occur with exposures, especially in small children.
    E) WITH THERAPEUTIC USE
    1) ADVERSE EFFECTS: Adverse events include gastrointestinal symptoms such as nausea, vomiting, belching, and flatulence from oral exposures and mild electrolyte abnormalities (hypokalemia, hypocalcemia, hypernatremia) and metabolic alkalosis.
    F) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Gastrointestinal symptoms are common, including nausea, vomiting, belching, flatulence, and gastric distention. Mild metabolic effects are possible, including alkalosis, hypocalcemia, hypokalemia and hypernatremia with associated dizziness, weakness, and irritability.
    2) SEVERE TOXICITY: Severe alkalemia may result in impaired oxygen release from hemoglobin, hypocalcemia tetany, paradoxical intracellular acidosis (from elevated pCO2), and hypokalemia. Hypernatremia and hyperosmolality can cause seizures and coma. Excessive sodium bicarbonate may also cause congestive heart failure exacerbation and pulmonary edema. Electrolyte abnormalities secondary to sodium bicarbonate administration may lead to QT prolongation and cardiac dysrhythmias. Severe gastric distention can rarely lead to stomach rupture with severe abdominal pain and hematemesis. Parenteral sodium bicarbonate extravasation may lead to tissue inflammation and necrosis. Inhalational exposures may cause pulmonary irritation, especially if exposed to higher concentrations as in some fire extinguishers. Dermal and eye exposures may cause some mild irritation.
    0.2.20) REPRODUCTIVE
    A) Sodium bicarbonate is not known to affect human reproduction.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, no studies regarding the potential carcinogenic effects of sodium bicarbonate in humans or experimental animals have been found.

Laboratory Monitoring

    A) Monitor serum electrolytes and renal function. In symptomatic patients or those with metabolic alkalosis monitor arterial or venous pH, urinary electrolytes and pH, and ECG.
    B) Depending on the patient's symptoms and electrolyte abnormalities, continuous cardiac monitoring, pulse oximetry, mental status checks, and head CT may be indicated.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) For mild or moderate exposures, supportive care is the mainstay of treatment. Correct electrolyte abnormalities. Irrigate exposed eyes. Wash exposed skin. Administer inhaled beta agonists for bronchospasm.
    2) INHALATION: Move the patient from the toxic environment to fresh air. Supportive care with supplemental oxygen and assisted ventilation as needed. Patients that develop bronchospasm can be treated with inhaled beta adrenergic agonists.
    3) PARENTERAL: Aspirate as much fluid from the aria as possible before removing the IV catheter. Extravasation injuries may require close monitoring and supportive care for pain and tissue injury. Severe extravasation that leads to tissue inflammation/necrosis or compartment syndromes may require surgical intervention.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) For patients with severe toxicity, supportive care is the mainstay of treatment. Hypotension can be treated with fluid boluses and pressors as necessary. Electrolyte abnormalities may be corrected as needed, but care must be taken not to correct serum sodium levels too quickly (which may cause seizures). Administration of 5% dextrose and half normal to NS with rates of administration usually at 2/3 of daily maintenance is critical. In addition, supplementation of potassium may be necessary. Acetazolamide may selectively correct alkalosis by promoting urinary bicarbonate excretion. However, it should NOT be used if serum potassium is less than 3.5 mEq/L. Treat seizures by correcting electrolyte abnormalities and administering benzodiazepines, add propofol or barbiturates if seizures persist or recur.
    C) DECONTAMINATION
    1) PREHOSPITAL: GI decontamination is not indicated. Irrigate exposed eyes. Wash skin with soap and water.
    2) HOSPITAL: GI decontamination is not indicated. Irrigate exposed eyes. Wash skin with soap and water.
    D) METABOLIC ALKALOSIS
    1) Most patients do well with gradual correction of their metabolic acidosis by administration of a combination of 0.9% saline and 0.45% saline and intravenous potassium repletion. In patients with very severe alkalemia (pH greater than 7.6 in unstable patients not responding to hydration), therapy with ammonium chloride or dilute HCl may be considered, but this is rarely necessary. Ammonium chloride diluted in NS may be given IV over 12 to 24 hours. This requires close monitoring of blood pH, electrolytes, and BUN. The dose is calculated by determining the hydrogen ion deficit and bicarbonate excess using the following formula: serum HCO3 level minus normal HCO3 level x 0.5 x body weight (kg) = amount of acid needed. Alternatively, one may treat SEVERE alkalemia with dilute (0.1 normal) HCl through a central venous catheter. HCl should be given as a 0.1 NS in 1 L of 5% dextrose or 0.225% sodium chloride IV over 6 to 24 hours at a rate of 10 mEq/hr up to 100 mEq/day. The dose calculated should be the same as listed above for ammonium chloride.
    E) VENTRICULAR DYSRHYTHMIAS
    1) Primary treatment is correction of electrolyte abnormalities, particularly hypokalemia. Institute continuous cardiac monitoring and obtain an ECG. Evaluate for electrolyte abnormalities (particularly hypokalemia, hypocalcemia, and hypomagnesemia) and correct as needed. Lidocaine and amiodarone are general first line agents for stable monomorphic ventricular tachycardia.
    F) ACUTE LUNG INJURY
    1) Maintain adequate ventilation and oxygenation with appropriate monitoring. If a patient does develop acute lung injury, ventilation with small tidal volumes (6 mL/kg) is preferred. Antibiotics are only indicated when there is evidence of infection. Experimental therapies include partial liquid ventilation and the use of calfactant.
    G) CEREBRAL EDEMA
    1) For patients with cerebral edema and elevated intracranial pressure, emergent treatment includes head elevation, administration of mannitol, and hyperventilation if there is evidence of herniation. Monitoring intracranial pressures, cerebral perfusion pressures, and cerebral blood flow may be needed. Mechanical decompression with ventriculostomy with CSF drainage, or craniectomy may be useful.
    H) ANTIDOTE
    1) There is no specific antidote for sodium bicarbonate.
    I) ENHANCED ELIMINATION
    1) Hemodialysis may be considered for seriously ill patients, especially those with renal insufficiency, with the use of high chloride, low acetate dialysate to remove bicarbonate and sodium and replace chloride deficits when other measures are ineffective.
    J) PATIENT DISPOSITION
    1) HOME CRITERIA: Older children or adults with unintentional ingestions with minimal to no symptoms may be managed at home.
    2) OBSERVATION CRITERIA: Patients should be sent to a healthcare facility if their exposure to sodium bicarbonate was a self-harm attempt or if the patient is symptomatic. They should be observed for 4 to 6 hours and be clearly improving or asymptomatic prior to discharge. Electrolytes should also be within normal limits or normalizing. In young children, minimal exposures can be symptomatic so any such exposures should be sent in for observation and lab work.
    3) ADMISSION CRITERIA: Patients with severe symptoms or getting worse after an observation period of 4 to 6 hours should be admitted to the hospital. Depending on the severity of their symptoms, ICU admission may be warranted (eg, for intubated patients or patients with severe metabolic or electrolyte abnormalities). Patients should not be discharged until they are clearly improving or asymptomatic.
    4) CONSULT CRITERIA: Patients admitted to the ICU may require consult by a critical care specialists. A nephrologist may be helpful in managing metabolic and electrolyte abnormalities. Consult a medical toxicologist or poison center for patients with severe toxicity or in whom the diagnosis is unclear.
    K) PITFALLS
    1) Pitfalls include correcting sodium abnormalities too quickly, which may lead to more severe neurological symptoms such as seizures, and underestimated severity in very young children, in whom much smaller doses may lead to severe symptoms.
    L) PHARMACOKINETICS
    1) Well absorbed orally. Both sodium and bicarbonate ions are eliminated in the urine. Dermal absorption is less complete, but may be significant in infants, those with denuded skin, or when used under occlusive dressings. There is no protein binding.
    M) PREDISPOSING CONDITIONS
    1) Patients that may be more sensitive to adverse reactions to sodium bicarbonate include those with cirrhosis, edema, heart failure, peptic ulcer disease, and renal impairment. In addition, both the elderly and children under the age of 2 years may develop severe symptoms at lower doses. In addition, pregnant women should avoid sodium bicarbonate antacids due to their potential to cause metabolic alkalosis and fluid overload.
    N) DIFFERENTIAL DIAGNOSIS
    1) Other substances that can cause hypernatremia (eg, NaCl) or strong bases that can cause metabolic alkalosis (eg, NaOH, however, a strong caustic reaction from NaOH is also likely to occur and would NOT be observed with sodium bicarbonate).

Range Of Toxicity

    A) Baking soda products contain 41.8 mEq (952 mg) of sodium (0.952 g) and 41.8 mEq of bicarbonate per teaspoonful.
    B) ADULT EXPOSURE: Adults with normal renal function can tolerate up to 1700 mEq daily with minimal symptoms. Alkalosis occurred in 10% of patients treated with 380 mEq sodium bicarbonate/day in combination with calcium carbonate. PEDIATRIC EXPOSURE: Life-threatening alkalosis has occurred after one tablespoonful (15 mL) in a 4 month-old infant. Much larger amounts are needed to cause hypernatremia (10 to 20 g/kg). In terms of lethal hypernatremia (serum Na greater than 185 mEq/L), it is estimated that a 3-year-old child would have to ingest about 4 tablespoonfuls/day for 10 days. DERMAL EXPOSURE: Topical application of sodium bicarbonate to denuded perineum resulted in toxicity to a 7 week old infant.
    C) THERAPEUTIC DOSE: Doses in adults and children vary depending on the route of administration and indication. In cardiac arrest, typical doses are in the 1 mEq/kg/dose range and repeated doses are guided by arterial blood gases. In hyperkalemia, initial dose IV is 50 mEq over 5 minutes. In patients with chronic renal failure with plasma HCO3 less than 15 mEq/L, initial doses start with 20 to 6 mEq/day in divided doses. In patients with renal tubular acidosis, oral doses range from 0.5 to 0 mEq/kg/day. Adult antacid dosing is from 325 mg to 2 g up to 4 times a day.

Clinical Effects

Summary Of Exposure

    A) USES: Sodium bicarbonate is used to treat metabolic acidosis, hyperkalemia, to treat QRS widening and dysrhythmias resulting from drugs that cause sodium channel blockade, to prevent contrast-induce nephropathy, and to alkalinize the urine. It is also present in antacids, mouthwash and baking soda. It is also an additive in meat processing and used to clean and neutralize acidity in vegetables.
    B) PHARMACOLOGY: Sodium bicarbonate dissociates to provide bicarbonate ions. Bicarbonate neutralizes hydrogen ion concentration and raises blood and urinary pH. Dissociated sodium ions help to overcome sodium channel blockade from certain sodium channel blocking drugs.
    C) TOXICOLOGY: Toxic effects from sodium bicarbonate are secondary to the sodium and bicarbonate ions which causes hypernatremia, alkalosis, and other secondary effects.
    D) EPIDEMIOLOGY: Sodium bicarbonate is extremely common in the environment and potential exposures are very common but rarely serious. Indeed, it is given as a treatment for many seriously ill patients. However, fatalities, though very rare, can occur with exposures, especially in small children.
    E) WITH THERAPEUTIC USE
    1) ADVERSE EFFECTS: Adverse events include gastrointestinal symptoms such as nausea, vomiting, belching, and flatulence from oral exposures and mild electrolyte abnormalities (hypokalemia, hypocalcemia, hypernatremia) and metabolic alkalosis.
    F) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Gastrointestinal symptoms are common, including nausea, vomiting, belching, flatulence, and gastric distention. Mild metabolic effects are possible, including alkalosis, hypocalcemia, hypokalemia and hypernatremia with associated dizziness, weakness, and irritability.
    2) SEVERE TOXICITY: Severe alkalemia may result in impaired oxygen release from hemoglobin, hypocalcemia tetany, paradoxical intracellular acidosis (from elevated pCO2), and hypokalemia. Hypernatremia and hyperosmolality can cause seizures and coma. Excessive sodium bicarbonate may also cause congestive heart failure exacerbation and pulmonary edema. Electrolyte abnormalities secondary to sodium bicarbonate administration may lead to QT prolongation and cardiac dysrhythmias. Severe gastric distention can rarely lead to stomach rupture with severe abdominal pain and hematemesis. Parenteral sodium bicarbonate extravasation may lead to tissue inflammation and necrosis. Inhalational exposures may cause pulmonary irritation, especially if exposed to higher concentrations as in some fire extinguishers. Dermal and eye exposures may cause some mild irritation.

Heent

    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) CORNEAL IRRITATION: No corneal irritation was found in rabbits eyes after a three hour continuous instillation of sodium bicarbonate solution (Grant & Schuman, 1993).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) HYPERTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) Hypertension may occur with chronic abuse (Johnson, 1989; Fitzgibbons & Snoey, 1999).
    B) HYPOTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) Hypotension may result from hypernatremia.
    b) CASE REPORT: A patient with viral pneumonia, acute respiratory and renal failure and metabolic acidosis was administered 100 mL of 8.4% sodium bicarbonate on 3 separate occasions. On each of the 3 occasions, a reduction in left ventricular stroke work was observed. In 2 of the 3 occasions hypotension and decreased cardiac output were observed (Cooper & Worthley, 1987).
    C) TACHYARRHYTHMIA
    1) WITH POISONING/EXPOSURE
    a) Tachycardia may result from hypernatremia.
    D) VENTRICULAR ARRHYTHMIA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 39-year-old man presented with syncope, multiple premature ventricular contractions and a wide complex tachycardia that responded to lidocaine. Metabolic derangements included hyponatremia, hypokalemia, hypochloridemia, metabolic alkalosis and alkalemia (pH 7.56). The patient improved with lidocaine administration, hydration, magnesium and potassium replacement (Fitzgibbons & Snoey, 1999).
    E) ELECTROCARDIOGRAM ABNORMAL
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: After taking approximately 2 tablespoons/day of baking soda for 2 days, a 35-year-old man with a history of a combined kidney-pancreas transplant for type I diabetes, developed bilateral tingling in hands and feet, pulling of the jaw, increased motor tone in the upper extremities, a positive Trousseau's sign in both arms, hypocalcemia, metabolic acidosis and a prolonged QT interval (Razavi, 2000).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) ALBUMINURIA
    1) WITH POISONING/EXPOSURE
    a) No permanent renal damage has been reported. Increased BUN, albuminuria, and casts have been noted in cases of alkalosis, and are reversible upon correction of acid-base imbalance. Albuminuria and BUN changes may persist for several weeks.

Acid-Base

    3.11.2) CLINICAL EFFECTS
    A) ALKALOSIS
    1) WITH POISONING/EXPOSURE
    a) HYPOKALEMIC HYPOCHLOREMIC METABOLIC ALKALOSIS: EARLY SYMPTOMS of alkalosis are weakness, dizziness, headache, dry mouth, and occasionally mental confusion and nervousness. Onset is generally 4 to 10 days after chronic ingestion.
    b) CASE REPORT: Alkalosis is rare in adults with normal renal function, however, extreme alkalosis has been described in a patient with mild chronic renal failure after ingestion of 2 pounds over a 2 week period (Levin, 1983).
    c) HYPOKALEMIC METABOLIC ALKALOSIS developed in a 35-year-old man after ingesting 2L of Gaviscon(R) (antacid preparation) over the preceding 48 hours prior to admission for epigastric pain. The patient was comatose with an initial Glasgow Coma Score of 3/15. Arterial blood gases on room air were: pH 7.45, HCO3 50.6 mmol/L (50.6 mEq/L), PO2 11 kPa (82.5 mmHg), and pCO2 8 kPa (60 mmHg). Serum potassium was 1.6 mmol/L, chloride 66 mmol/L, and serum sodium was 127 mmol/L. A toxicology screen was negative. Treatment included sedation, mechanical ventilation and 1L of 0.9% saline over 1 hour followed by 240 mmols KCl over 24 hours in 0.9% saline. The patient was extubated within the hour and gradually improved over the next 24 hours. No long term effects were reported (Gawarammana et al, 2007).
    d) CASE REPORT: After taking approximately 2 tablespoons/day of baking soda for 2 days, a 35-year-old man with a history of a combined kidney-pancreas transplant for type I diabetes, developed bilateral tingling in hands and feet, pulling of the jaw, increased motor tone in the upper extremities, a positive Trousseau's sign in both arms, and a prolonged QT interval. Laboratory results showed sodium 143 mEq/L, potassium 3.6 mEq/L, chloride 95 mEq/L, bicarbonate 38 mEq/L, blood urea nitrogen 25 mg/dL, creatinine 1.9 mg/dL, phosphorus 4.0 mg/dL, calcium 7.8 mg/dL, ionized calcium 3.7 mg/dL (normal 4.5 to 5.6 mg/dL), albumin 3.5 g/dL; urine pH greater than 9.0; arterial blood gases, pH 7.52, pCO2 49 mmHg, pO2 63 mmHg, a bicarbonate 40 mEq/L. He was treated with normal saline hydration and recovered (Razavi, 2000).
    e) HYPOKALEMIC HYPOCHLOREMIC METABOLIC ALKALOSIS occurred in one infant following 1 tablespoonful given parenterally, and in infants following topical application of liberal amounts to denuded skin for diaper rash for 1 week (Lacroix & Chicoine, 1982; Gonzalez & Hogg, 1981a).
    f) HYPOKALEMIC METABOLIC ALKALOSIS: A 21-year-old woman consuming 50 to 150 g sodium bicarbonate daily for a feeling of well-being and alleviation of tension developed hypokalemia (1.8 to 2.2 mmol/L) with plasma bicarbonate concentrations greater than 40 mmol/L. Attempts at withdrawal produced discomfort and craving (Linford & James, 1986).
    g) CASE REPORT: An 11-day-old infant developed fever, alkalosis, hypernatremia, apnea, and multiple episodes of generalized tonic-clonic seizures after ingesting baking soda contaminated formula. A CT scan of the head showed cerebral edema. Laboratory results revealed white blood cell count of 23,300/mm(3), sodium 187 mmol/L, bicarbonate 44 mmol/L, and pH 7.95. To prevent colic, the patient's grandmother had been mixing 2 scoops of baking soda with 2 ounces of water in the child's formula and also dipped the milk-bottle's nipples in baking soda. Following supportive therapy (isotonic fluids, phenobarbital, acetazolamide), she recovered completely and was discharged 6 days after admission (Bryant et al, 2002).
    h) HYPOKALEMIC HYPOCHLOREMIC METABOLIC ALKALOSIS: A 65-year-old man with a history of chronic foot ulcers, developed severe hypokalemic metabolic alkalosis after applying baking soda to his foot and ingesting a "palmful" of baking soda daily for more than a year. He had a blood pH of 7.65 with hypochloremia (73 mEq/L), hypokalemia (1.8 mEq/L), and prerenal azotemia. Treatment included multiple liters of isotonic saline with potassium replacement; total doses included 7 L of 0.9% saline, 19 L of 0.45% saline, 960 mEq of KCl over several days. The patient was briefly intubated for an altered mental status (agitation). Electrolytes normalized along with pH; no permanent sequelae occurred (John et al, 2012).
    i) ACUTE-ON-CHRONIC TOXICITY
    1) CASE REPORTS: Hypokalemic hypochloremic metabolic alkalosis has been reported in adults who chronically ingested baking soda for dyspepsia (Thomas & Stone, 1994; Fitzgibbons & Snoey, 1999). The patients were treated with intravenous fluid and electrolyte replacement. Despite patient education, two patients were readmitted with similar symptoms within weeks of the first episode.

Endocrine

    3.16.2) CLINICAL EFFECTS
    A) HYPERGLYCEMIA
    1) WITH POISONING/EXPOSURE
    a) Hyperglycemia secondary to hypernatremic dehydration has been reported.
    B) ADRENAL CORTICAL HYPOFUNCTION
    1) WITH POISONING/EXPOSURE
    a) HYPORENINEMIC HYPOALDOSTERONISM with hyperkalemia and hyponatremia may occur as a rebound effect following withdrawal from chronic high-dose ingestion.

Reproductive

    3.20.1) SUMMARY
    A) Sodium bicarbonate is not known to affect human reproduction.
    3.20.2) TERATOGENICITY
    A) ANIMAL STUDIES
    1) Sodium bicarbonate was not teratogenic in rats, mice or rabbits (Shardein, 2000; Food and Drug Research Labs, 1974).
    3.20.3) EFFECTS IN PREGNANCY
    A) HUMANS
    1) Sodium bicarbonate is beneficial to human reproduction. In a study of 93 infertile couples, douching with a bicarbonate solution before intercourse improved the conception rate (Ansari, 1980). Injection or infusion of sodium bicarbonate has been used to treat fetal hypoxic stress (Klimenko PA et al, 1983; Neumark, 1981), fetal acidosis (Hamilton & Behrman, 1972), to prevent maternal netabolic acidosis during labor (Ron-El et al, 1980), and to improve the acid-base balance in normal full-term infants (Clark, 1971).
    2) While the use of antacids is a common practice during pregnancy, one source advised against using sodium bicarbonate for this purpose (Bishop, 1978), presumably to minimize the problem of sodium retention. Sodium bicarbonate has been used as an ingredient of a vaginal spermicide as an effervescent agent (Marcus BJ, 1980) but is not harmful when in direct contact with sperm.

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS144-55-8 (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) At the time of this review, no studies regarding the potential carcinogenic effects of sodium bicarbonate in humans or experimental animals have been found.

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) CYANOSIS
    1) WITH POISONING/EXPOSURE
    a) Cyanosis has occurred secondary to metabolic alkalosis.
    B) IRRITATION SYMPTOM
    1) WITH POISONING/EXPOSURE
    a) Pulmonary irritation may occur if breathed in high concentrations, as in some fire extinguishers.
    C) ACUTE LUNG INJURY
    1) WITH POISONING/EXPOSURE
    a) Pulmonary edema may be observed.

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) FATIGUE
    1) WITH POISONING/EXPOSURE
    a) Weakness or irritability may be initial symptoms.
    B) DIZZINESS
    1) WITH POISONING/EXPOSURE
    a) Dizziness may be an early symptom (Thomas & Stone, 1994; Fitzgibbons & Snoey, 1999).
    C) CLOUDED CONSCIOUSNESS
    1) WITH POISONING/EXPOSURE
    a) Mental confusion may be observed.
    D) PARESTHESIA
    1) WITH POISONING/EXPOSURE
    a) Paresthesias may occur secondary to hypocalcemia.
    b) CASE REPORT: After taking approximately 2 tablespoons/day of baking soda for 2 days, a 35-year-old man with a history of a combined kidney-pancreas transplant for type I diabetes, developed bilateral tingling in hands and feet, pulling of the jaw, increased motor tone in the upper extremities, a positive Trousseau's sign in both arms, and a prolonged QT interval (Razavi, 2000).
    E) TINNITUS
    1) WITH POISONING/EXPOSURE
    a) Tinnitus may be an initial symptom.
    F) NEUROPATHY
    1) WITH POISONING/EXPOSURE
    a) Neurological changes may result from hypernatremia, hypocalcemia, or alkalosis. Severe hypernatremia may result in irreversible neurological damage.
    G) COMA
    1) WITH POISONING/EXPOSURE
    a) Progressive obtundation and coma may occur in severe toxicity.
    H) CEREBRAL EDEMA
    1) WITH POISONING/EXPOSURE
    a) Cerebral edema may occur in severe toxicity.
    b) CASE REPORT: An 11-day-old infant developed fever, alkalosis, severe hypernatremia (187 mmol/L), apnea, and multiple episodes of generalized tonic-clonic seizures after ingesting formula adulterated with baking soda. A CT scan of the head showed cerebral edema. Following supportive therapy, she recovered completely and was discharged 6 days after admission (Bryant et al, 2002).
    I) SEIZURE
    1) WITH POISONING/EXPOSURE
    a) Seizures may occur with severe toxicity.
    b) CASE REPORT: An 11-day-old infant developed fever, alkalosis, hypernatremia, apnea, and multiple episodes of generalized tonic-clonic seizures after ingesting formula adulterated with baking soda. A CT scan of the head showed cerebral edema. Laboratory results revealed white blood cell count of 23,300/mm(3), sodium 187 mmol/L, bicarbonate 44 mmol/L, and pH 7.95. To prevent colic, the patient's grandmother mixed 2 scoops of baking soda with 2 ounces of water in the child's formula and also dipped the milk-bottle's nipples in baking soda. Following supportive therapy, she recovered completely and was discharged 6 days after admission (Bryant et al, 2002).
    J) TETANY
    1) WITH POISONING/EXPOSURE
    a) Tetany may occur secondary to hypocalcemia in severe toxicity.
    b) CASE REPORT: After taking approximately 2 tablespoons/day of baking soda for 2 days, a 35-year-old man with a history of a combined kidney-pancreas transplant for type I diabetes, developed bilateral tingling in hands and feet, pulling of the jaw, increased motor tone in the upper extremities, a positive Trousseau's sign in both arms, and a prolonged QT interval. Ionized calcium was 3.7 mg/dL (normal 4.5 to 5.6 mg/dL), blood gases pH 7.52, pCO2 49 mm Hg, bicarbonate 40 mEq/L (Razavi, 2000).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) ABDOMINAL PAIN
    1) WITH POISONING/EXPOSURE
    a) Abdominal pain, bloating and abdominal distension may occur.
    B) INJURY OF STOMACH
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 46-year-old man inadvertently ingested approximately 250 mL of a solution containing potassium carbonate and sodium bicarbonate and despite self-induced vomiting he began to have abdominal discomfort and tenderness. Laboratory studies were within normal limits. He was started on pain medications and IV ondansetron. A litmus test of the solution revealed a pH of 10. Based on those findings, an endoscopy was performed and showed grade 1 linear mucosal injury to the body and antrum of the stomach. He was treated with famotidine and discharged the following day with minimal symptoms (Scott et al, 2011).
    C) GASTRIC ULCER WITH PERFORATION
    1) WITH POISONING/EXPOSURE
    a) Spontaneous rupture of the stomach has occurred rarely following ingestion of sodium bicarbonate after excessive eating or drinking.
    b) The occurrence of severe, sharp abdominal pain and hematemesis are indications for immediate surgical consultation.
    c) Upon examination, rigid and tender abdomen, shock, prostration, and absence of peristalsis may be seen (Murdfield, 1926; Lemmon & Paschal, 1941; Kregel, 1955) (Zer et al, 1970) (Lazebnik et al, 1986).
    d) CASE REPORT: A 10-month-old child who died from complications related to hypernatremia had an infarcted distended stomach that was herniated into the left chest at postmortem, presumably from sodium bicarbonate (Robertson, 1988).

Genotoxicity

    A) At the time of this review, no studies regarding the potential genetic effects of sodium bicarbonate have been found.
    B) It is a component of most culture media used for growing mammalian cells and is not expected to have any adverse genetic effects at physiological concentrations.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor serum electrolytes and renal function. In symptomatic patients or those with metabolic alkalosis monitor arterial or venous pH, urinary electrolytes and pH, and ECG.
    B) Depending on the patient's symptoms and electrolyte abnormalities, continuous cardiac monitoring, pulse oximetry, mental status checks, and head CT may be indicated.
    4.1.2) SERUM/BLOOD
    A) ACID/BASE
    1) Monitor arterial or venous blood gases (blood pH, total CO2) in patients with metabolic alkalosis.
    B) BLOOD/SERUM CHEMISTRY
    1) Monitor electrolytes, renal function, and glucose.
    4.1.3) URINE
    A) OTHER
    1) Urinary electrolytes and pH should be determined.
    B) URINALYSIS
    1) Obtain urinalysis.
    a) In unexplained metabolic alkalosis, alkaline urine (pH greater than or equal to 7.5) with high urine anion gap (greater than 50 mEq/L) can suggest surreptitious vomiting or alkali ingestion (eg, baking soda) while a low urine pH (less than or equal to 6.0) with a low urine anion gap (less than 50 mEq/L) can be due to other causes (eg, diuretic or laxative abuse) (Yi et al, 2012).
    C) SPOT URINE CHLORIDE TEST
    1) In unexplained metabolic alkalosis, a spot urine chloride test of less than 10 mEq/L with alkalosis can suggest diuretic administration, laxative abuse, or surreptitious alkali ingestion (eg, baking soda) (Yi et al, 2012).
    4.1.4) OTHER
    A) OTHER
    1) MONITORING
    a) Monitor ECG when alkalosis is present. Monitor renal function.

Treatment

Monitoring

    A) Monitor serum electrolytes and renal function. In symptomatic patients or those with metabolic alkalosis monitor arterial or venous pH, urinary electrolytes and pH, and ECG.
    B) Depending on the patient's symptoms and electrolyte abnormalities, continuous cardiac monitoring, pulse oximetry, mental status checks, and head CT may be indicated.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) ACTIVATED CHARCOAL
    1) Activated charcoal has NOT been shown to effectively adsorb sodium bicarbonate.
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) Activated charcoal has NOT been shown to effectively adsorb sodium bicarbonate.
    6.5.3) TREATMENT
    A) SEIZURE
    1) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    2) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    3) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    4) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).
    5) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    6) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    B) HYPOTENSIVE EPISODE
    1) SUMMARY
    a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
    2) DOPAMINE
    a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    3) NOREPINEPHRINE
    a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
    b) DOSE
    1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
    2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).
    C) FLUID/ELECTROLYTE BALANCE REGULATION
    1) Administer 5% dextrose and 0.45% to 0.9% sodium chloride in amounts calculated to lower serum sodium no sooner than 24 to 36 hours after initiation of infusion. The rate of administration is critical (usually 2/3 of daily maintenance).
    2) If the drop in serum sodium occurs more rapidly, seizures are likely to ensue. Potassium chloride 40 mEq/L should be added to the infusion and administered over 2 to 4 hours.
    D) ACETAZOLAMIDE
    1) May selectively correct alkalosis by promoting urinary bicarbonate excretion. DO NOT USE if serum potassium is less than 3.5 mEq/L (DOSE: 250 to 500 mg orally or IV every 6 to 12 hours).
    E) METABOLIC ALKALOSIS
    1) Most patients do well with gradual correction of their metabolic acidosis by administration of a combination of 0.9% saline and 0.45% saline and intravenous potassium repletion. In patients with very severe alkalemia (pH greater than 7.6 in unstable patients not responding to hydration), therapy with ammonium chloride or dilute HCl may be considered, but this is rarely necessary.
    2) AMMONIUM CHLORIDE: Administer ammonium chloride diluted in normal saline IV over 12 to 24 hours. The dose is calculated by determining the hydrogen ion deficit and bicarbonate excess using the following formula:
    a) Serum HCO3 level minus normal HCO3 level x 0.5 x body weight in kilograms = amount of acid needed. Closely and repeatedly monitor blood pH, electrolytes and BUN.
    3) HCL: Alternatively, SEVERE ALKALEMIA may be treated with dilute (0.1 Normal) hydrochloric acid through a central venous catheter
    a) DOSE: 0.1 Normal solution in 1 liter of 5% dextrose or 0.225% sodium chloride solution IV over 6 to 24 hours; at a rate of 10 mEq/hour up to 100 mEq/day.
    b) The dose can be calculated using the same formula as for ammonium chloride.
    F) VENTRICULAR ARRHYTHMIA
    1) Primary treatment is correction of electrolyte abnormalities, particularly hypokalemia.
    2) VENTRICULAR DYSRHYTHMIAS SUMMARY
    a) Obtain an ECG, institute continuous cardiac monitoring and administer oxygen. Evaluate for hypoxia, acidosis, and electrolyte disorders (particularly hypokalemia, hypocalcemia, and hypomagnesemia). Lidocaine and amiodarone are generally first line agents for stable monomorphic ventricular tachycardia, particularly in patients with underlying impaired cardiac function. Amiodarone should be used with caution if a substance that prolongs the QT interval and/or causes torsades de pointes is involved in the overdose. Unstable rhythms require immediate cardioversion.
    3) LIDOCAINE
    a) LIDOCAINE/INDICATIONS
    1) Ventricular tachycardia or ventricular fibrillation (Prod Info Lidocaine HCl intravenous injection solution, 2006; Neumar et al, 2010a; Vanden Hoek et al, 2010).
    b) LIDOCAINE/DOSE
    1) ADULT: 1 to 1.5 milligrams/kilogram via intravenous push. For refractory VT/VF an additional bolus of 0.5 to 0.75 milligram/kilogram can be given at 5 to 10 minute intervals to a maximum dose of 3 milligrams/kilogram (Neumar et al, 2010a). Only bolus therapy is recommended during cardiac arrest.
    a) Once circulation has been restored begin a maintenance infusion of 1 to 4 milligrams per minute. If dysrhythmias recur during infusion repeat 0.5 milligram/kilogram bolus and increase the infusion rate incrementally (maximal infusion rate is 4 milligrams/minute) (Neumar et al, 2010a).
    2) CHILD: 1 milligram/kilogram initial bolus IV/IO; followed by a continuous infusion of 20 to 50 micrograms/kilogram/minute (de Caen et al, 2015).
    c) LIDOCAINE/MAJOR ADVERSE REACTIONS
    1) Paresthesias; muscle twitching; confusion; slurred speech; seizures; respiratory depression or arrest; bradycardia; coma. May cause significant AV block or worsen pre-existing block. Prophylactic pacemaker may be required in the face of bifascicular, second degree, or third degree heart block (Prod Info Lidocaine HCl intravenous injection solution, 2006; Neumar et al, 2010a).
    d) LIDOCAINE/MONITORING PARAMETERS
    1) Monitor ECG continuously; plasma concentrations as indicated (Prod Info Lidocaine HCl intravenous injection solution, 2006).
    4) AMIODARONE
    a) AMIODARONE/INDICATIONS
    1) Effective for the control of hemodynamically stable monomorphic ventricular tachycardia. Also recommended for pulseless ventricular tachycardia or ventricular fibrillation in cardiac arrest unresponsive to CPR, defibrillation and vasopressor therapy (Link et al, 2015; Neumar et al, 2010a). It should be used with caution when the ingestion involves agents known to cause QTc prolongation, such as fluoroquinolones, macrolide antibiotics or azoles, and when ECG reveals QT prolongation suspected to be secondary to overdose (Prod Info Cordarone(R) oral tablets, 2015).
    b) AMIODARONE/ADULT DOSE
    1) For ventricular fibrillation or pulseless VT unresponsive to CPR, defibrillation, and a vasopressor therapy give an initial dose of 300 mg IV followed by 1 dose of 150 mg IV. For stable ventricular tachycardias: Infuse 150 milligrams over 10 minutes, and repeat if necessary. Follow by a 1 milligram/minute infusion for 6 hours, then a 0.5 milligram/minute. Maximum total dose over 24 hours is 2.2 grams (Neumar et al, 2010a).
    c) AMIODARONE/PEDIATRIC DOSE
    1) Infuse 5 milligrams/kilogram as a bolus for pulseless ventricular tachycardia or ventricular fibrillation; may repeat twice up to 15 mg/kg. Infuse 5 milligrams/kilogram over 20 to 60 minutes for perfusing tachycardias. Maximum single dose is 300 mg. Routine use with other drugs that prolong the QT interval is NOT recommended (Kleinman et al, 2010).
    d) ADVERSE EFFECTS
    1) Hypotension and bradycardia are the most common adverse effects (Neumar et al, 2010a).
    G) ACUTE LUNG INJURY
    1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
    2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).
    a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)
    3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
    4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
    5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
    6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
    7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).
    H) CEREBRAL EDEMA
    1) CLINICAL IMPLICATIONS
    a) Cerebral edema and elevated intracranial pressure (ICP) may occur. Emergent management includes head elevation and administration of mannitol; hyperventilation should be performed if there is evidence of impending herniation.
    2) MONITORING
    a) Patients will usually require endotracheal intubation and mechanical ventilation. Monitor intracranial pressure, cerebral perfusion pressure and cerebral blood flow.
    3) TREATMENT
    a) Most information on the treatment of cerebral edema is derived from studies of traumatic brain injury.
    4) MANNITOL
    a) ADULT/PEDIATRIC DOSE: 0.25 to 1 gram/kilogram intravenously over 10 to 15 minutes (None Listed, 2000).
    b) AVAILABLE FORMS: Mannitol injection (5%, 10%, 15%, 20%, 25%).
    c) MAJOR ADVERSE REACTIONS: Congestive heart failure, hypernatremia, hyponatremia, hyperkalemia, renal failure, pulmonary edema, and allergic reactions.
    d) PRECAUTIONS: Contraindicated in well-established anuria or impaired renal function not responding to a test dose, pulmonary edema, CHF, severe dehydration; caution in progressive oliguria and azotemia. Do not add to whole blood for transfusions; enhanced neuromuscular blockade has occurred with tubocurarine. Keep serum osmolarity below 320 mOsm.
    e) MONITORING PARAMETERS: Renal function, urine output, fluid balance, serum potassium levels, serum osmolarity, and CVP.
    5) HYPERTONIC SALINE
    a) Preliminary studies suggest that hypertonic saline (7.5% saline/6% dextran) 100 ml reduced ICP more effectively than 200 mL of 20% mannitol in adults with elevated ICP after traumatic brain injury(Battison et al, 2005).
    6) ELEVATION
    a) Elevation of the head of the bed to approximately 30 degrees decreases ICP and improves cerebral perfusion pressure (Meixensberger et al, 1997; Schneider et al, 1993; Feldman et al, 1992).
    7) MECHANICAL DECOMPRESSION
    a) Early surgical decompression, ventriculostomy with CSF drainage, or craniectomy may be useful in patients with persistent elevation of ICP (Sahuquillo & Arikan, 2006; Sakai et al, 1998; Polin et al, 1997; Taylor et al, 2001). Most experience with these modalities has been in patients with traumatic brain injury.
    8) HYPERVENTILATION
    a) SUMMARY: Hyperventilation has been associated with adverse outcomes and should not be performed routinely (Muizelaar et al, 1991). It is indicated in patients who have clinical evidence of herniation or if there is intracranial hypertension refractory to sedation, paralysis, CSF drainage and osmotic diuretics (None Listed, 2000a).
    b) RECOMMENDATION:
    1) The PCO2 must be controlled in the range of 25 torr; further lowering of PCO2 may create undesirable effects secondary to local tissue hypoxia.
    2) End-tidal CO2 tension, correlated with an initial ABG measurement, provides a noninvasive means of monitoring PCO2 (Mackersie & Karagianes, 1990).
    3) Most authorities advise that hyperventilation should be considered a temporizing measure only; SUSTAINED hyperventilation should be avoided (Am Acad Neurol, 1997; Bullock et al, 1996; Kirkpatrick, 1997).

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.

Eye Exposure

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

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Enhanced Elimination

    A) HEMODIALYSIS
    1) Consider high chloride, low acetate dialysate to remove bicarbonate and replace chloride deficit when other measures are ineffective or in patients with renal insufficiency.

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 severe symptoms or getting worse after an observation period of 4 to 6 hours should be admitted to the hospital. Depending on the severity of their symptoms, ICU admission may be warranted (eg, for intubated patients or patients with severe metabolic or electrolyte abnormalities). Patients should not be discharged until they are clearly improving or asymptomatic.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Older children or adults with unintentional ingestions with minimal to no symptoms may be managed at home.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Patients admitted to the ICU may require consult by a critical care specialists. A nephrologist may be helpful in managing metabolic and electrolyte abnormalities. Consult a medical toxicologist or poison center for patients with severe toxicity or in whom the diagnosis is unclear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients should be sent to a healthcare facility if their exposure to sodium bicarbonate was in a self-harm attempt or if the patient is symptomatic. They should be observed for 4 to 6 hours and be clearly improving or asymptomatic prior to discharge. Electrolytes should also be within normal limits or normalizing. In young children, minimal exposures can be symptomatic so any such exposures should be sent in for observation and lab work.

Abstracts

Case Reports

    A) INFANT
    1) TOPICAL: The application of sodium bicarbonate to denuded perineum resulted in toxicity in a 7-week-old infant (Lacroix & Chicoine, 1982).
    B) ADULT
    1) ORAL: An 84-year-old with adult onset diabetes, hypertension, and ischemic heart disease was given 3 "Mayo" enemas over a 16-hour period diluted to 1 L each. A "Mayo" enema is made up of 120 mL brown sugar plus 105 mL of sodium bicarbonate in 125 mL of water. Dose is one daily. The patient became agitated and disoriented with stool and urinary incontinence. Intestinal ileus developed, as well as septic phlebitis, UTI, sepsis, and decubitus ulcers. The patient died. Serum Na went from 139 mmol/L to 130 mmol/L, potassium from 4.6 mmol/L to 4.9 mmol/L (Huang & Bergman, 1990).

Range Of Toxicity

Summary

    A) Baking soda products contain 41.8 mEq (952 mg) of sodium (0.952 g) and 41.8 mEq of bicarbonate per teaspoonful.
    B) ADULT EXPOSURE: Adults with normal renal function can tolerate up to 1700 mEq daily with minimal symptoms. Alkalosis occurred in 10% of patients treated with 380 mEq sodium bicarbonate/day in combination with calcium carbonate. PEDIATRIC EXPOSURE: Life-threatening alkalosis has occurred after one tablespoonful (15 mL) in a 4 month-old infant. Much larger amounts are needed to cause hypernatremia (10 to 20 g/kg). In terms of lethal hypernatremia (serum Na greater than 185 mEq/L), it is estimated that a 3-year-old child would have to ingest about 4 tablespoonfuls/day for 10 days. DERMAL EXPOSURE: Topical application of sodium bicarbonate to denuded perineum resulted in toxicity to a 7 week old infant.
    C) THERAPEUTIC DOSE: Doses in adults and children vary depending on the route of administration and indication. In cardiac arrest, typical doses are in the 1 mEq/kg/dose range and repeated doses are guided by arterial blood gases. In hyperkalemia, initial dose IV is 50 mEq over 5 minutes. In patients with chronic renal failure with plasma HCO3 less than 15 mEq/L, initial doses start with 20 to 6 mEq/day in divided doses. In patients with renal tubular acidosis, oral doses range from 0.5 to 0 mEq/kg/day. Adult antacid dosing is from 325 mg to 2 g up to 4 times a day.

Therapeutic Dose

    7.2.1) ADULT
    A) ORAL
    1) ADULTS 60 YEARS OF AGE AND OLDER: 650 to 1300 mg (1 to 2 tablets) every 4 hours. MAXIMUM DOSE: Should not exceed 7800 mg (12 tablets) in 24 hours (Prod Info sodium bicarbonate oral tablets, 2008)
    2) ADULTS LESS THAN 60 YEARS OF AGE: 650 to 2600 mg (1 to 4 tablets) every 4 hours. MAXIMUM DOSE: Should not exceed 15,600 mg (24 tablets) in 24 hours (Prod Info sodium bicarbonate oral tablets, 2008).
    B) CARDIAC ARREST
    1) Routine use no longer recommended by American Heart Association during cardiopulmonary resuscitation (Neumar et al, 2010)
    2) May be beneficial in certain circumstances, such as preexisting metabolic acidosis, hyperkalemia, or tricyclic antidepressant overdose (Neumar et al, 2010)
    3) Routine use of sodium bicarbonate in cardiac arrest is not recommended. When used in special situation, the typical initial dose is 1 mEq/kg, and then the dosage should be guide by the bicarbonate concentration or calculated base deficit from blood gas analysis or laboratory measurement (Neumar et al, 2010).
    7.2.2) PEDIATRIC
    A) RESUSCITATION: PALS GUIDELINES
    1) INTRAVENOUS OR INTRAOSSEOUS: The usual dose is 1 to 2 mEq/kg IV/IO slowly after adequate ventilation; may repeat every 5 to 10 minutes until pH is greater than 7.45 (Kleinman et al, 2010; Prod Info sodium bicarbonate IV injection, 2006).
    B) METABOLIC ACIDOSIS WITH NORMAL ANION GAP
    1) DOSAGE BASED ON BASE DEFICIT: HCO3 needed (mEq) = HCO3 deficit (mEq/L) x (0.3 x body wt (kg)).
    2) Administer half of the calculated dose then assess need for remainder (Andrade et al, 2007). May give IV or orally.
    3) IF BASE DEFICIT UNKNOWN: Older children, 2 to 5 mEq/kg IV over 4 to 8 hours (Prod Info sodium bicarbonate IV injection, 2006).
    C) TRICYCLIC ANTIDEPRESSANT OVERDOSE
    1) The usual dose is 1 to 2 mEq/kg IV boluses every 5 to 10 minutes until pH is greater than 7.45, followed by a sodium bicarbonate infusion (150 mEq sodium bicarbonate per liter of D5W) to maintain alkalosis (Kleinman et al, 2010).

Minimum Lethal Exposure

    A) SUMMARY
    1) Death from hypernatremia is a frequent occurrence when serum sodium rises above 185 milliequivalents/liter.
    B) CASE REPORTS
    1) CASE REPORT: As a rough estimate, a 3-year-old child (with an estimated 10 L extracellular fluid volume) would have to ingest about 4 tablespoonfuls to achieve this level (from 135 to 185 mEq/L).
    2) CASE REPORT: However, life-threatening alkalosis has been reported in a 4-month-old child after ingestion of 1 tablespoonful.

Maximum Tolerated Exposure

    A) SUMMARY
    1) Ingestion of 10 to 20 g/kg will produce hypernatremia in the majority of patients.
    2) Alkalosis is uncommon unless ingestion is chronic and renal function is impaired: following 25 mEq/kg/day for 3 weeks in adults, plasma CO2 increased by only 5 mEq/L with weight gain as the predominant effect (van Goidsenhoven et al, 1954).
    B) CASE REPORTS
    1) ADULT
    a) Alkalosis occurred in 10% of 1350 patients treated with 380 mEq/day in combination with calcium carbonate 640 mEq/day (Kirsner & Palmer, 1942).
    b) BICARBONATE: Ingestion of soluble Panadol(R) containing 18 millimoles of bicarbonate per tablet, 8 tablets/day, resulted in hypokalemic metabolic alkalosis in a 29-year-old woman with impaired renal function (Acomb et al, 1987).
    c) ANTACID PREPARATION: Severe hypochloremic (chloride 66 mmol/L), hypokalemic (potassium 1.6 mmol/L), metabolic alkalosis (pH 7.54) occurred in a 35-year-old man after ingesting 2L of Gaviscon(R), an antacid preparation, over 48 hours. The patient was admitted with a Glasgow Coma Score of 3/15 and recovered quickly with supportive care (Gawarammana et al, 2007).
    d) BAKING SODA: A 65-year-old man developed a mixed acid-base disorder with a pH of 7.69, hypochloremia, hypokalemia and prerenal azotemia following chronic use of baking soda. The patient admitted to daily ingestion of a "palmful" of baking soda and covering a foot ulcer with baking soda and wrapping it in plastic daily for a 1.5 years. He responded to isotonic saline and potassium supplementation for his metabolic alkalosis (primary disorder) (John et al, 2012).
    e) BAKING SODA: A 68-year-old man with a history of poorly managed COPD and chronic epigastric pain, developed severe hyponatremia (sodium 121 mEq/L), hypochloremia (chloride 53 mEq/L) hypokalemia (potassium 1.7 mEq/L) and metabolic alkalosis following the chronic use of baking soda. Mechanical ventilation was needed for respiratory failure. He recovered completely following IV fluids and electrolyte replacement and was started on a proton pump inhibitor for an ulcer (Ajbani et al, 2011).
    2) PEDIATRIC
    a) Hypernatremia without alkalosis was noted in a 3-year-old girl following ingestion of 8 to 10 tablespoonfuls/day for 10 days.
    3) INFANT
    a) Topical application of sodium bicarbonate to denuded perineum resulted in toxicity in a 7-week-old infant (Lacroix & Chicoine, 1982).

Workplace Standards

    A) ACGIH TLV Values for CAS144-55-8 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS144-55-8 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS144-55-8 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) 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
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS144-55-8 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Physicochemical

Physical Characteristics

    A) white crystalline powder or granules (Budavari, 1996)

Ph

    A) 8.3 (for a freshly prepared 0.1 M solution) (Budavari, 1996)

Molecular Weight

    A) 84.01 (Budavari, 1996)

References

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