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SORBITOL

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) The primary therapeutic use is as an osmotic cathartic, frequently used in toxic emergencies to hasten the elimination of activated charcoal and therefore also of ingested toxins.
    B) Conflicting opinions exist as to its therapeutic efficacy and importance as an adjunct with activated charcoal in the management of poisoning emergencies (McNamara et al, 1988; Keller et al, 1989).
    C) Its other significant use is as a non-cariogenic sweetener in sugar-free and dietetic candies and gum.
    1) Additionally, it is used as a palatability enhancer, viscosity-inducer, humectant, solution stabilizer, source of carbohydrates, plasticizer in gelatin capsules, and to reduce the crystallization effect in syrups.
    2) Sorbitol has been shown to enhance the palatability of charcoal but not more so than sucrose or saccharin (Cooney, 1980).
    D) Several commercially available charcoal preparations come premixed with sorbitol (see Available Forms section).

Specific Substances

    1) D-glucitol
    2) D-sorbitol
    3) Glucitol
    4) Slomin
    5) Sorbit
    6) Sorbite
    7) Sorbo
    8) Sorbol
    9) Sorbostyl
    1.2.1) MOLECULAR FORMULA
    1) C6H14O6 (Prod Info sorbitol urologic irrigating solution, 3.3%, 2003)

Available Forms Sources

    A) FORMS
    1) Sorbitol is contained in several activated charcoal products. The amount of sorbitol varies. Sorbitol, USP contains 70% w/w, equivalent to 89.7 grams per 100 mL (89.7% w/v) of mixture (using specific gravity = 1.285).
    2) In several studies using charcoal/sorbitol mixtures, the amount of sorbitol was erroneously calculated as a w/v percentage (Minocha et al, 1985a; Krenzelok et al, 1985).
    Trade Name/ ManufacturerSorbitol (grams)Activated Charcoal (grams)Package size (mL)
    Acta-Char (Med Corp)6250240
    Actidose4825120
    *Actidose (Paddock)9650240
    Charcoaid (Requa)11130150
    Charcolex (Lex)1840200
    **Super-Char (Gulf) Biosystems)6230240
    *Prior to 1986 this product contained 192 g/240 mL of sorbitol
    **No longer marketed

    B) SOURCES
    1) Sorbitol is found in a wide range of products. The more common forms of sugar-free products and their general concentrations are listed below (Hyams, 1982).
    FormulationSorbitol Content
    Gum1.2 to 2.2 g/piece
    Mints1.4 g/piece
    Bars5 to 7 g
    Wafers2.8 to 4.4 g

    C) USES
    1) A survey of emergency departments in the New York City area showed that 39 percent of departments usually administer sorbitol with multiple dose activated charcoal therapy as part of routine management of poisonings.
    a) This places patients at risk of fluid and electrolyte disorders (Wax et al, 1991).
    2) Numerous pharmaceutical preparations such as expectorants, elixirs, syrups and topical agents contain sorbitol. Some toothpastes contain as much as 30% sorbitol. Sugar-free children's chewable multiple vitamins may also contain significant amounts of sorbitol.
    3) Adults with constipation problems may be placed on 70% sorbitol solutions for maintenance therapy (Lederle et al, 1990).
    4) Sorbitol is ubiquitous and is regarded by the Food and Drug Administration as an inactive ingredient (Brown, 1983). The World Health Organization states that sorbitol does not represent a health hazard and the establishment of an accepted daily intake was deemed unnecessary (WHO, 1978).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) WITH THERAPEUTIC USE
    1) Abdominal cramping and diarrhea are the most common effects from use of sorbitol. Emesis may also occur, but less commonly. Fluid and electrolyte imbalance may result from excessive catharsis.
    2) Other adverse effects are secondary to fluid and electrolyte imbalance resulting from excessive catharsis (dehydration, electrolyte abnormalities, hypotension, elevated serum osmolality) or possibly absorption.
    3) Death has occurred in patients with a rare autosomal recessive genetic intolerance to fructose, following the parenteral administration of sorbitol.
    4) Vital signs should not be affected following the therapeutic or inadvertent excessive use of sorbitol. Only in extreme cases where excessive diarrhea has produced fluid and electrolyte imbalance can aberrations in vital signs be anticipated.
    B) WITH POISONING/EXPOSURE
    1) Abdominal cramping and diarrhea are the most common effects from overuse or use of sorbitol. Emesis may also occur, but less commonly. Fluid and electrolyte imbalance may result from excessive catharsis.
    2) Other adverse effects are secondary to fluid and electrolyte imbalance resulting from excessive catharsis (dehydration, electrolyte abnormalities, hypotension, elevated serum osmolality) or possibly absorption.
    3) SEVERE HYPERNATREMIC DEHYDRATION has been described in a 3-month-old receiving 220 mL of a 70% w/w sorbitol/charcoal combination (89.7% w/v). The use of multiple dose cathartics including sorbitol is not recommended.
    4) Vital signs should not be affected following inadvertent excessive use of sorbitol. Only in extreme cases where excessive diarrhea has produced fluid and electrolyte imbalance can aberrations in vital signs be anticipated.
    0.2.5) CARDIOVASCULAR
    A) WITH THERAPEUTIC USE
    1) Cardiac dysrhythmias and hypotension may occur in conjunction with electrolyte imbalance.
    0.2.8) GASTROINTESTINAL
    A) WITH THERAPEUTIC USE
    1) Emesis occurs occasionally following ingestion of sorbitol/activated charcoal mixtures.
    2) Catharsis may persist for 8 to 12 hours or longer.
    B) WITH POISONING/EXPOSURE
    1) Dose-related osmotic catharsis, abdominal cramping, and diarrhea may occur within 24 minutes of ingestion.
    0.2.12) FLUID-ELECTROLYTE
    A) WITH THERAPEUTIC USE
    1) Excessive catharsis may result in dehydration and electrolyte imbalance. Elevations of serum glucose and serum osmolality are theoretically possible after administration of sorbitol.
    0.2.20) REPRODUCTIVE
    A) Sorbitol is classified as FDA pregnancy category C. There are no data regarding the effects of sorbitol on pregnancy or breastfeeding.
    B) No teratogenic effects have been observed in either rabbits or rats, although duration of gestation was increased and litter size decreased in rats.

Laboratory Monitoring

    A) The diagnosis of sorbitol induced toxicity is clinical and historical. Qualitative confirmation in feces can be made but is not readily available. Breath hydrogen analysis resulting in expired breath hydrogen of greater than 10 ppm may help substantiate, but not confirm diagnosis.
    B) Monitor fluid, electrolyte and serum osmolarity as indicated by clinical chemistry to confirm the adverse effects associated with sorbitol.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) ACTIVATED CHARCOAL: Activated charcoal does not inhibit the cathartic effect of sorbitol and is not recommended after accidental ingestion of sorbitol. Activated charcoal will not render sorbitol ineffective since it does not compromise its gastrointestinal osmotic effects.
    B) Oral rehydration and electrolyte replacement is usually sufficient. In severe intoxication aggressive parenteral fluid/electrolyte replacement may be necessary.
    C) Serum electrolytes and osmolality should be assessed frequently.
    D) Severe cases may mandate cardiovascular monitoring.

Range Of Toxicity

    A) The threshold of laxative effect appears to be around 0.5 gram/kg in children. Abdominal cramping may occur with as little as 0.3 g/kg.
    B) Ingestions of as little as 10 g may cause flatulence and bloating; 20 g can cause abdominal cramping, and at least 50 grams appears to be necessary to produce purgative effects in most adults.
    C) In a small study, 3 adults were able to tolerate doses of up to 110 grams/day.

Clinical Effects

Summary Of Exposure

    A) WITH THERAPEUTIC USE
    1) Abdominal cramping and diarrhea are the most common effects from use of sorbitol. Emesis may also occur, but less commonly. Fluid and electrolyte imbalance may result from excessive catharsis.
    2) Other adverse effects are secondary to fluid and electrolyte imbalance resulting from excessive catharsis (dehydration, electrolyte abnormalities, hypotension, elevated serum osmolality) or possibly absorption.
    3) Death has occurred in patients with a rare autosomal recessive genetic intolerance to fructose, following the parenteral administration of sorbitol.
    4) Vital signs should not be affected following the therapeutic or inadvertent excessive use of sorbitol. Only in extreme cases where excessive diarrhea has produced fluid and electrolyte imbalance can aberrations in vital signs be anticipated.
    B) WITH POISONING/EXPOSURE
    1) Abdominal cramping and diarrhea are the most common effects from overuse or use of sorbitol. Emesis may also occur, but less commonly. Fluid and electrolyte imbalance may result from excessive catharsis.
    2) Other adverse effects are secondary to fluid and electrolyte imbalance resulting from excessive catharsis (dehydration, electrolyte abnormalities, hypotension, elevated serum osmolality) or possibly absorption.
    3) SEVERE HYPERNATREMIC DEHYDRATION has been described in a 3-month-old receiving 220 mL of a 70% w/w sorbitol/charcoal combination (89.7% w/v). The use of multiple dose cathartics including sorbitol is not recommended.
    4) Vital signs should not be affected following inadvertent excessive use of sorbitol. Only in extreme cases where excessive diarrhea has produced fluid and electrolyte imbalance can aberrations in vital signs be anticipated.

Vital Signs

    3.3.3) TEMPERATURE
    A) WITH THERAPEUTIC USE
    1) HYPERTHERMIA may be expected to develop in cases where severe dehydration has occurred.

Heent

    3.4.2) HEAD
    A) WITH THERAPEUTIC USE
    1) Excessive dehydration in very young children may result in fontanelle depression.
    3.4.3) EYES
    A) WITH THERAPEUTIC USE
    1) The eyes may appear sunken if extreme dehydration has occurred. Unlike galactose, chronic sorbitol use is not associated with cataract formation (Grant, 1986).

Cardiovascular

    3.5.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Cardiac dysrhythmias and hypotension may occur in conjunction with electrolyte imbalance.
    3.5.2) CLINICAL EFFECTS
    A) CONDUCTION DISORDER OF THE HEART
    1) WITH THERAPEUTIC USE
    a) Cardiac arrhythmias and hypotension may occur if sorbitol has produced excessive catharsis resulting in dehydration and electrolyte imbalance.

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) TOXIC ENCEPHALOPATHY
    1) WITH THERAPEUTIC USE
    a) CASE REPORT - A 55-year-old female with a history of esophagitis had a gastroduodenostomy and fundoplication performed, and was started on parenteral nutrition which included 50 g sorbitol, 200 g xylitol and 200 g fructose and 100 g glucose/day (approximately 6 g/kg/day sugar surrogates for 26 days)(Heye et al, 1991). The patient's renal and neurological status began to gradually decline and seizures developed with diffuse cerebral dysfunction.
    1) The patient died 23 days after admission due to increased intracranial pressure and cerebral damage. The authors suggested that the development of encephalitis was due to calcium oxalate crystals (oxalosis) formed by the sugar surrogates.

Gastrointestinal

    3.8.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Emesis occurs occasionally following ingestion of sorbitol/activated charcoal mixtures.
    2) Catharsis may persist for 8 to 12 hours or longer.
    B) WITH POISONING/EXPOSURE
    1) Dose-related osmotic catharsis, abdominal cramping, and diarrhea may occur within 24 minutes of ingestion.
    3.8.2) CLINICAL EFFECTS
    A) DIARRHEA
    1) WITH THERAPEUTIC USE
    a) Osmotic diarrhea has been reported following the ingestion of "sugar-free" candies in both children and an adult (MMWR, 1984; (Breitenbach & Simon, 1994).
    b) Following a therapeutic dose with activated charcoal, catharsis should ensue in an average of 1.0 to 1.5 hours and persist for 8 to 12 hours, with prolonged catharsis up to 33 hours being reported (Minocha et al, 1985a; Krenzelok et al, 1985).
    1) Toxins which decrease gastric motility such as those with anticholinergic properties and narcotics may delay the onset of catharsis by several hours (Harchelroad & Krenzelok, 1987).
    c) CASE SERIES - Administration of 30 mL of a 70% w/w sorbitol solution (89.7% w/v) caused watery diarrhea in 5 of 5 volunteers two to three hours later. The efficacy of sorbitol as a purgative has resulted in its popularity in the treatment of overdose patients.
    1) However, the safety and efficacy of cathartics for the treatment of drug overdose has been questioned.
    d) CASE SERIES - Bloating, abdominal pain, and diarrhea occurred in 7 of 42 volunteers who received 10 grams of sorbitol (Jain et al, 1985).
    e) CASE SERIES - A study was conducted in healthy adult human volunteers who ingested sorbitol 100 grams with activated charcoal 30 grams.
    1) Severe prolonged diarrhea resulted, but no significant changes in serum electrolytes, serum osmolality, BUN, or metabolic profile as compared to controls were noted (Minocha et al, 1985a).
    f) CHRONIC TOXICITY - Persistent severe diarrhea has been reported in two adults receiving oral medications (valproic acid, theophylline) in a sorbitol base (Hill et al, 1991; Shelly, 1993). In both cases, the symptoms lasted for approximately 1 to 6 months and resulted in prolonged hospitalization in one case; all symptoms stopped 1 to 3 days after the medications were changed.
    g) Pneumatosis intestinalis was reported in a child with profound developmental delay and a seizure disorder who received all of his medications in liquid form with sorbitol as a common ingredient (Duncan et al, 1997). The child had a history of chronic, persistent, unexplained diarrhea. After stool cultures were negative, all medications were changed to tablet/pill form and symptoms gradually improved; a normal abdominal x-ray was reported 10 months later.
    2) WITH POISONING/EXPOSURE
    a) SUMMARY - Sorbitol is poorly absorbed in overdose and produces a dose-related osmotic catharsis resulting in the development of abdominal cramping and diarrhea, which may occur as soon as 24 minutes after ingestion (Krenzelok et al, 1985).
    b) CASE SERIES - Children aged 5 to 13 years ingested 3 to 16 pieces of sorbitol-containing dietetic candy, containing 3 grams/piece and developed diarrhea 30 to 90 minutes after ingestion with recovery in 2 to 3 hours (MMWR, 1984).
    c) CASE REPORT - A 24-month-old male developed abdominal distention, cramping and explosive diarrhea 2 hours after eating the contents of one package of dietetic mints containing 9.3 grams of sorbitol. Ten stools occurred over 4 hours (Gryboski, 1966).
    d) CASE REPORT - In another case of osmotic diarrhea, a patient had a 7-year history of abdominal pain and diarrhea diagnosed as irritable bowel syndrome and presented with abdominal pain and watery bowel movements up to 10 times a day. After osmotic diarrhea was confirmed and physical examination and laboratory results gave no indication as to the etiology of the diarrhea, the patient was questioned further. It was then found that the patient consumed 60 sticks of sugar-free gum daily, with each stick containing approximately 1.25#g of sorbitol, giving a total dose of 75#g/day. A dose as low as 10#g is capable of producing a clinical effect (Greaves et al, 1996).
    B) VOMITING
    1) WITH THERAPEUTIC USE
    a) CASE SERIES - Five of 8 subjects who participated in a bioavailability study and ingested a 70% sorbitol solution developed severe and protracted emesis. When the 70% sorbitol was admixed with activated charcoal 50 grams only one of eight developed vomiting (Massanari, 1987).
    2) WITH POISONING/EXPOSURE
    a) Emesis may occur following the ingestion of large amounts of sorbitol. One study revealed an incidence of 9% following the ingestion of sorbitol 192 grams and activated charcoal 50 grams in adults.
    1) Several additional research subjects complained of nausea, but emesis did not occur (Krenzelok et al, 1985).
    2) Two additional studies in humans using 100 to 192 grams of sorbitol with activated charcoal failed to report emesis as an adverse effect (Minocha et al, 1985a; Krenzelok et al, 1985).
    b) A survey of clinical toxicologists regarding cathartic use revealed that emesis occurred occasionally when sorbitol 70% w/w (89.7% w/v) was used with activated charcoal (Riegel & Becker, 1981).
    c) CASE SERIES - In a study of 68 overdose patients treated with activated charcoal and sorbitol 19 (27.9%) vomited the activated charcoal within 30 minutes of its administration (Harchelroad & Krenzelok, 1987).
    C) MALABSORPTION SYNDROME
    1) WITH THERAPEUTIC USE
    a) Chronic use of sorbitol, resulting in excessive catharsis, may result in the malabsorption of fat, bile acids and fat-soluble vitamins (Hill & Kamath, 1982).
    b) Individuals with malabsorption syndromes may be extremely sensitive to very small doses of sorbitol (Jain, 1985; (Jain et al, 1987; Rumessen & Gudmand-Hoyer, 1988). Sorbitol is NOT advised in these individuals.
    D) VASCULAR INSUFFICIENCY OF INTESTINE
    1) WITH THERAPEUTIC USE
    a) CASE SERIES - Five patients receiving sodium polystyrene sulfonate in sorbitol enemas developed colonic necrosis; four of the five patients died (Lillemore et al, 1987).
    b) INCIDENCE - In a case series of 752 patients who had received sodium polystyrene sulfonate (SPS), 117 had been exposed within one week of having surgery. Two (1.8%) cases of intestinal necrosis were associated with SPS in sorbitol (Gerstman et al, 1992).
    c) CASE REPORT - Wootton et al (1989) also reported extensive colonic necrosis in a renal transplant recipient who received 4 enemas of sodium polystyrene sulfonate and sorbitol. Sorbitol appears to be toxic to colonic mucosa.
    d) Burnett (1990) stated that the package insert for sodium polystyrene sulfonate suspension recommends that the colon be extensively flushed following the use of this product. It is unclear whether this recommendation was followed in the above cases.
    e) CASE REPORT - Bowel perforation and subsequent peritonitis led to death in a 55-year-old woman given aggressive cathartic therapy for treatment of aspirin overdose. She received 4 doses of magnesium sulfate (total 120 g) and 6 doses of sorbitol (total amount unspecified) (Brent et al, 1989).
    2) ANIMAL STUDIES - Rat studies also demonstrated transneural necrosis from the use of 70% sorbitol alone in the enema solution.
    E) ABDOMINAL PAIN
    1) WITH THERAPEUTIC USE
    a) CASE SERIES - 20 of 42 normal subjects developed abdominal cramping and/or bloating after the ingestion of sorbitol 10 grams (Jain et al, 1987). Abdominal pain developed in a four-year-old after the ingestion of 0.3 gram/kg (Hyams, 1982).
    b) CASE SERIES - Seven of 25 individuals with functional bowel disorder developed mild to moderate discomfort after the ingestion of 5 grams of sorbitol (Rumessen & Gudmand-Hoyer, 1988).
    c) CASE SERIES - Thirty-six of 124 subjects without diagnosed gastrointestinal disease developed bloating and/or abdominal cramps after a 10 gram test dose of sorbitol.
    F) INTESTINAL OBSTRUCTION
    1) WITH THERAPEUTIC USE
    a) CASE SERIES - INTESTINAL PSEUDO-OBSTRUCTION with gross distension of the large and small intestine was described in 2 patients (1 fatality) following 4 oral doses of activated charcoal (50 g) in 150 mL of 70% sorbitol (every 4 hours), to treat severe theophylline overdose (Longdon & Henderson, 1992).
    1) A direct relationship between sorbitol and intestinal pseudo-obstruction was not established.

Genitourinary

    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) URINE ABNORMAL
    a) RATS - ACIDURIA has been reported in rats that were fed large amounts of sorbitol. High daily doses in humans does not produce aciduria (Hamalainen, 1987).

Acid-Base

    3.11.2) CLINICAL EFFECTS
    A) LACTIC ACIDOSIS
    1) WITH THERAPEUTIC USE
    a) Lactic acidosis has been reported following prolonged intravenous infusions of sorbitol (Reynolds, 1982).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) THROMBOPHLEBITIS
    1) WITH THERAPEUTIC USE
    a) Thrombophlebitis has been reported following prolonged intravenous infusion (Reynolds, 1982). No hematologic abnormalities were noted in healthy adult human volunteers who ingested sorbitol 84 grams (Minocha et al, 1985a).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) SKIN IRRITATION
    1) LACK OF EFFECT
    a) WITH THERAPEUTIC USE
    1) There is no evidence that topical application of sorbitol is irritating to the skin or produces hypersensitivity reactions. Numerous topical preparations such as lotions and creams contain sorbitol.

Endocrine

    3.16.2) CLINICAL EFFECTS
    A) ADRENAL CORTICAL HYPOFUNCTION
    1) WITH THERAPEUTIC USE
    a) There is no evidence to suggest that acute or chronic use of sorbitol has detrimental endocrine effects in humans.
    b) Since insulin is not necessary for the transport of sorbitol intracellularly, reasonable amounts can be safely used by diabetics (Brunzell, 1978).
    2) ANIMAL STUDIES - Long-term feeding studies performed in rats who ingested 20% of their daily intake as sorbitol resulted in unilateral and bilateral hyperplasia of the adrenal medulla as well as a decrease in thyroid gland weight (WHO, 1978).
    B) HYPERGLYCEMIA
    1) WITH THERAPEUTIC USE
    a) CASE SERIES - Thirty-five grams of sorbitol administered to adult volunteers elevated the blood sugar by 9 to 49 mg/dL only in diabetic patients.
    1) Sorbitol concentrations in blood could not be measured in most subjects (detection limit 2 to 3 mg/dL), but in one healthy volunteer it was 9 mg/dL (Adcock & Gray, 1957).
    C) LACK OF EFFECT
    1) WITH THERAPEUTIC USE
    a) Diabetic children are able to assimilate and tolerate dietary sorbitol without developing hyperglycemia or glucosuria (Steinke et al, 1961).
    b) The intake of sorbitol by diabetics is limited by the osmotic cathartic effect. Intravenous infusion of up to 297 grams of sorbitol over 28 hours has not resulted in hyperglycemia (Bye, 1969).

Reproductive

    3.20.1) SUMMARY
    A) Sorbitol is classified as FDA pregnancy category C. There are no data regarding the effects of sorbitol on pregnancy or breastfeeding.
    B) No teratogenic effects have been observed in either rabbits or rats, although duration of gestation was increased and litter size decreased in rats.
    3.20.2) TERATOGENICITY
    A) LACK OF EFFECT
    1) In rats fed a diet of 20% sorbitol, the duration of gestation was increased and litter sizes were reduced. No teratogenic effects have been observed in either rabbits or rats (WHO, 1978).
    B) ANIMAL STUDIES
    1) There are no animal reproduction studies on the use of sorbitol (Prod Info sorbitol urologic irrigating solution, 3.3%, 2003).
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to sorbitol during pregnancy in humans (Prod Info sorbitol urologic irrigating solution, 3.3%, 2003).
    B) PREGNANCY CATEGORY
    1) Sorbitol is classified by the manufacturer as FDA pregnancy category C (Prod Info sorbitol urologic irrigating solution, 3.3%, 2003).
    C) ANIMAL STUDIES
    1) There are no animal reproduction studies on the use of sorbitol (Prod Info sorbitol urologic irrigating solution, 3.3%, 2003).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to sorbitol during lactation in humans (Prod Info sorbitol urologic irrigating solution, 3.3%, 2003).
    B) BREAST MILK
    1) Sorbitol is slowly and incompletely absorbed from the gastrointestinal tract and metabolized to fructose. There is probably only minimal risk associated with its use while breast feeding. It is conceivable that excessive use of sorbitol by a breastfeeding mother could produce diarrhea in an infant.
    3.20.5) FERTILITY
    A) ANIMAL STUDIES
    1) There are no animal fertility studies on the use of sorbitol (Prod Info sorbitol urologic irrigating solution, 3.3%, 2003).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) The diagnosis of sorbitol induced toxicity is clinical and historical. Qualitative confirmation in feces can be made but is not readily available. Breath hydrogen analysis resulting in expired breath hydrogen of greater than 10 ppm may help substantiate, but not confirm diagnosis.
    B) Monitor fluid, electrolyte and serum osmolarity as indicated by clinical chemistry to confirm the adverse effects associated with sorbitol.

Methods

    A) OTHER
    1) The diagnosis of sorbitol-induced toxicity is a clinical and historical diagnosis. Since sorbitol may be present in feces, qualitative confirmation can be made, but most facilities do not have an assay readily available for this purpose.
    2) Malabsorbed sorbitol is fermented by colonic bacteria and generates hydrogen gas.
    a) Therefore, breath hydrogen analysis resulting in expired breath hydrogen of greater than 10 ppm may help substantiate but not confirm a diagnosis of sorbitol toxicity (Hyams, 1982; Rumessen & Gudmand-Hoyer, 1988).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) If diarrhea occurring secondary to ingesting sorbitol-containing substances such as candy, gum, pharmaceuticals, etc, is severe and not self-limiting, especially in children, emergency department evaluation is recommended.
    B) Patients with severe protracted diarrhea or who have demonstrated dehydration and/or electrolyte abnormalities should be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Self-limited abdominal cramping and diarrhea can be treated in the home with rest and clear liquid replacement.

Monitoring

    A) The diagnosis of sorbitol induced toxicity is clinical and historical. Qualitative confirmation in feces can be made but is not readily available. Breath hydrogen analysis resulting in expired breath hydrogen of greater than 10 ppm may help substantiate, but not confirm diagnosis.
    B) Monitor fluid, electrolyte and serum osmolarity as indicated by clinical chemistry to confirm the adverse effects associated with sorbitol.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) ACTIVATED CHARCOAL
    1) Activated charcoal does not inhibit the cathartic effect of sorbitol (Minocha et al, 1985a; Krenzelok et al, 1985) and serves no role in the management of sorbitol overdose.
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) Activated charcoal does not inhibit the cathartic effect of sorbitol (Minocha et al, 1985a; Krenzelok et al, 1985) and serves no role in the management of sorbitol overdose.
    B) CATHARTIC
    1) Cathartics are contraindicated due to the strong purgative effect of sorbitol.
    6.5.3) TREATMENT
    A) FLUID/ELECTROLYTE BALANCE REGULATION
    1) If sufficient sorbitol has been ingested toxic sequelae may develop. Effects are usually self-limited and replacement of fluid and electrolyte losses should be sufficient therapy.
    2) In severe intoxication aggressive parenteral replacement of fluid and electrolytes may be necessary.
    B) MONITORING OF PATIENT
    1) Frequent assessment of serum electrolytes and osmolality should be performed.
    2) Severe cases may mandate cardiovascular monitoring.

Enhanced Elimination

    A) LACK OF EFFECT
    1) Since absorption is limited and sorbitol enhances its own elimination through catharsis, no other means of enhancing elimination are recommended.

Abstracts

Case Reports

    A) ACUTE EFFECTS
    1) A 55-year-old woman received magnesium sulfate 120 grams and 6 doses of sorbitol, along with activated charcoal, for treatment of an aspirin overdose. She became hypotensive and bradycardic with a magnesium level of 17.8 mEq/L 24 hours after admission.
    2) She stabilized after dialysis until the following day, when she developed an acute abdomen and died. Bowel perforation was documented at postmortem examination (Brent et al, 1989).
    B) ADULT
    1) A 23-year-old, 55-kg woman with a history of depression and a previous suicide attempt, intentionally ingested 50 phenobarbital tablets of 30 mg each (time lapse before admission not specified).
    2) On admission the patient's clinical indications were normal except for drowsiness and pulse of 120 bpm. While the gastric toxic screen returned negative, her urine toxic screen showed acetaminophen, ethanol, codeine, and phenobarbital.
    3) The patient was administered 1 mg of Narcan and 50 mL 50% dextrose in water intravenously. Cathartic treatment included 30 grams of activated charcoal in 150 mL 70% wt/vol sorbitol suspension, along with additional 30 mL doses of 70% sorbitol and 200 mL doses of magnesium citrate.
    4) This dosing was repeated every 3 hours for 27 hours with a total of nine doses of charcoal-sorbitol, seven 30-mL doses of 70% sorbitol alone, and three doses of magnesium citrate. Concomitantly the patient was infused with 0.9% saline in 5% dextrose at 200 mL/h for approximately 1,800 mL.
    5) At 12 hours after initiation of therapy, an increase in serum sodium to 163 mmol/L and a decrease in serum bicarbonate to 19 mmol/L were noted which led to institution of 0.45% saline in 5% dextrose with 45 mmol sodium bicarbonate per liter at 200 mL/h for a total of 1,800 mL.
    6) However, at 18 hours, the serum sodium had increased to 183 mmol/L with a body water deficit figured to be approximately 8 L.
    7) At that point the treatment was changed to provide infusion of 5% dextrose at a rapid rate, administration of 1,200 mL water via nasogastric tube and discontinuance of cathartic therapy. At 22 hours after hypernatremia had been noted, the electrolyte disorder was corrected.
    8) At 40 hours postadmission with a glucose reading of 43.1 mmol, 5 units of humulin regular insulin were intravenously infused while hypokalemia and nonanion-gap metabolic acidosis were treated with 260 mmol of potassium plus bicarbonate replacement.
    9) At 54 hours postadmission, the patient's vital signs were stable and she showed normal mental status and normal laboratory parameters.

Range Of Toxicity

Summary

    A) The threshold of laxative effect appears to be around 0.5 gram/kg in children. Abdominal cramping may occur with as little as 0.3 g/kg.
    B) Ingestions of as little as 10 g may cause flatulence and bloating; 20 g can cause abdominal cramping, and at least 50 grams appears to be necessary to produce purgative effects in most adults.
    C) In a small study, 3 adults were able to tolerate doses of up to 110 grams/day.

Therapeutic Dose

    7.2.1) ADULT
    A) LAXATIVE
    1) RECTAL, AGED 12 YEARS AND OVER: 120 mL of 25% to 30% solution (1 part sorbitol with 2.3 parts water) in a single daily dose for up to 1 week (OTC Product Information, as posted to the DailyMed site 07/2012).
    2) ADULT: A general therapeutic dose is 20 to 50 g in adults (Ellis & Krantz, 1941; S Sweetman , 2001); although lower doses may produce various effects (e.g., 10 g produced severe abdominal pain, bloating, and diarrhea in 7 of 42 adults) (Jain et al, 1985).
    3) MULTIPLE DOSE: Patients (especially pediatric) who received multiple dose activated charcoal therapy should NOT receive a dose of sorbitol with each dose of activated charcoal (Sullivan & Krenzelok, 1988; Farley, 1987).
    B) CATHARTIC
    1) WITH ACTIVATED CHARCOAL: The usual dose for adults of sorbitol is 1 to 2 g per kg of body weight (USPDI, 1999). Sorbitol content varies among the different preparations available; consult the product label to determine the amount of sorbitol (USPDI, 1999).
    2) NOTE: Use is NOT recommended for multiple-dose therapy because of the potential for excessive catharsis. The first dose should be administered with the first dose of activated charcoal. Do NOT give more than 1 or 2 doses of sorbitol within a 24 hour period (USPDI, 1999).
    3) STUDIES: Two studies showed that 100 and 192 g with activated charcoal 50 g produced a significant catharsis (Minocha et al, 1985a; Krenzelok et al, 1985). Additionally, a dosage of 1.5 to 3 g/kg has been recommended as a cathartic with activated charcoal (Minocha et al, 1985b). Repeated doses of the higher amount have resulted in hypernatremia (Caldwell et al, 1987).
    7.2.2) PEDIATRIC
    A) LAXATIVE
    1) RECTAL, AGED 12 YEARS AND OVER: 120 mL of 25% to 30% solution (1 part sorbitol with 2.3 parts water) in a single daily dose for up to 1 week (OTC Product Information, as posted to the DailyMed site 07/2012).
    2) RECTAL, UP TO 12 YEARS OF AGE: Safety and efficacy have not been established (OTC Product Information, as posted to the DailyMed site 07/2012).
    B) CATHARTIC
    1) NOTE: Not more than 1 or 2 doses of sorbitol should be administered within 24 hours. The first dose of sorbitol should be given with first dose of activated charcoal (USPDI, 1999).
    2) WITH ACTIVATED CHARCOAL: The usual dose of sorbitol 70% (90.15 g/100 mL) is 2 mL/kg of body weight, or a dose NOT to exceed 3 g of sorbitol per kg of body weight (USPDI, 1999). Sorbitol content varies among the different preparations available; consult the product label to determine the amount of sorbitol (USPDI, 1999).

Minimum Lethal Exposure

    A) CASE REPORTS
    1) Death secondary to bowel perforation was reported in a 55-year-old woman following administration of 120 grams of magnesium sulfate and 6 doses of sorbitol for treatment of an aspirin overdose (Brent et al, 1989).

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) Oral administration of sorbitol may result in increased osmotic pressure with as little as 10 grams of sorbitol causing flatulence and bloating; 20 grams may cause abdominal cramping and diarrhea, and total daily doses of 50 grams or greater may produce adverse GI effects in many adult patients (Lutomski et al, 1993).
    2) In one study, several adults were able to tolerate doses of up to 110 grams/day (Lutomski et al, 1993). Most tolerated an average of 71 grams/day before "unacceptable" side effects were produced.
    B) CASE REPORTS
    1) ADULT
    a) The amount of sorbitol found in 2 or more packages of breath fresheners can cause enough osmotic fluid balance changes to be responsible for hypotension in adults (Moore, 1988).
    b) Three adults developed hypernatremia after receiving 240 milliliters of 70 percent weight/weight sorbitol (192 grams) every 4 hours for 3, 4, and 6 doses, respectively (Caldwell et al, 1987). Severe hypernatremia was reported in another adult following a total of 210 milliliters of 70% sorbitol (Allerton & Strom, 1991).
    2) INFANT
    a) Electrolyte imbalance was observed in a 3-month-old child who received over 20 grams/kilogram of sorbitol (Farley, 1986).
    b) A 2-year-old child was treated with an activated charcoal-sorbitol product in a multiple dose regimen for an imipramine ingestion. The child became dehydrated and hypernatremic (McCord, 1987). Both problems are attributed to sorbitol-induced catharsis.

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Sorbitol produces osmotic catharsis by increasing intraluminal water volume. It also serves as a caloric source of carbohydrates. One gram of sorbitol yields 3.994 Kcal.
    1) Being 30 to 60% as sweet as cane sugar it also imparts sweetness and palatability. High concentrations of sorbitol have higher viscosity than glycerol, therefore sorbitol is used as a viscosity inducer.
    B) Sorbitol is partially metabolized by gut bacteria and has been shown to improve psychomotor function in cirrhosis (McClain et al, 1981).

Toxicologic Mechanism

    A) The primary toxic manifestation of ingested sorbitol is diarrhea. This is an extension of the pharmacologic effect of osmotic catharsis. Low doses may have a laxative effect whereas large doses produce a purgative effect.

Physicochemical

Physical Characteristics

    A) sweet, white solid form, clear liquid

Ph

    A) 5 to 7 (Prod Info sorbitol urologic irrigating solution, 3.3%, 2003)
    B) 4.5 to 6.5 (Prod Info sorbitol urologic irrigating solution, 3%, 2004)

Molecular Weight

    A) 182.17 (Prod Info sorbitol urologic irrigating solution, 3.3%, 2003)

References

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