Joseph Lister, often considered the father of modern surgery, revolutionized surgical treatment and dramatically reduced surgical mortality by introducing the concept of antisepsis to the surgical theatre.50 It was Lister’s understanding that microorganisms contributed to infection and sepsis from even the most trivial wounds that led to his search for chemicals that would prevent such infection. Lister demonstrated that phenol, a chemical that was used to treat foul-smelling sewage, could be used to clean dirty wounds of patients with compound fractures and dramatically increase survival rates. Soon thereafter, the use of phenol was expanded to surgical instrument cleaning and as a surgical hand scrub wash, ushering in the modern surgical era.
Antiseptics, disinfectants, and sterilants are a diverse group of germicides used to prevent the transmission of microorganisms to patients (Table 101–1). Although these terms are sometimes used interchangeably and some of these xenobiotics are used for both antisepsis and disinfection, the distinguishing characteristics between the groups are important to emphasize. An antiseptic is a chemical that is applied to living tissue to kill or inhibit microorganisms. Iodophors, chlorhexidine, and the alcohols (ethanol and isopropanol) are commonly used antiseptics. A disinfectant is a chemical that is applied to inanimate objects to kill microorganisms. Bleach (sodium hypochlorite), phenolic compounds, formaldehyde, hydrogen peroxide liquid, ortho-phthalaldehyde, and quaternary ammonium compounds are examples of currently used disinfectants. Neither antiseptics nor disinfectants have complete sporicidal activity. A sterilant is a chemical that is applied to inanimate objects to kill all microorganisms as well as spores. Ethylene oxide, glutaraldehyde, hydrogen peroxide gas, and peracetic acid are examples of sterilants. Many of the xenobiotics used to kill microorganisms also demonstrate considerable human toxicity.18,69,180
TABLE 101–1Antiseptics, Disinfectants, Sterilants, and Related Xenobiotics ||Download (.pdf) TABLE 101–1 Antiseptics, Disinfectants, Sterilants, and Related Xenobiotics
|Xenobiotic ||Commercial Product ||Use ||Toxic Effects ||Therapeutics and Evaluation |
| Boric acid ||Borax ||Antiseptic ||Blue-green emesis and diarrhea ||Orogastric lavage |
|Sodium perborate ||Mouthwash ||Boiled lobster appearance of skin ||Hemodialysis (rare) |
|Dobell solution ||Eyewash ||Central nervous system (CNS) depression; |
|Roach powder ||kidney failure |
| (Chaps. 76 and 106) || || || || |
| Ethanol ||Rubbing alcohol (70% ethanol) ||Antiseptic ||CNS depression ||Supportive |
|Disinfectant ||Respiratory depression |
|Dermal irritant |
| Isopropanol ||Rubbing alcohol (70% isopropanol) ||Antiseptic ||CNS depression ||Supportive |
|Disinfectant ||Respiratory depression ||Hemodialysis (rare) |
|Ketonemia, ketonuria |
|Hemorrhagic tracheobronchitis |
| Formaldehyde ||Formalin ||Disinfectant ||Caustic ||Orogastric lavage |
| ||(37% formaldehyde, 12%–15% methanol) || |
| Glutaraldehyde ||Cidex (2% glutaraldehyde) ||Sterilant ||Mucosal and dermal irritant ||Supportive |
| ortho-Phthalaldehyde (OPA) ||Cidex OPA (<1% OPA) ||Sterilant ||Mucosal and dermal irritant ||Supportive |
|Chlorinated Compounds |
| Chlorhexidine ||Hibiclens ||Antiseptic ||GI irritation ||Supportive |
| Chlorates ||Sodium chlorate ||Antiseptic (obsolete) ||Hemolysis ||Exchange transfusion |
|Potassium chlorate ||Matches ||Methemoglobinemia ||Hemodialysis |
|Herbicide ||Kidney failure |
| Chlorine ||Disinfectant ||Irritant ||Supportive |
| Chlorophors (sodium hypochlorite) ||Household bleach (5% NaOCl) ||Disinfectant ||Mild GI irritation ||Endoscopy (rare) |
|Dakin solution (1 part 5% NaOCl, 10 parts H2O) ||Decontaminating solution || || |
|Ethylene Oxide || ||Sterilant ||Irritant ||Supportive |
|Plasticizer ||CNS depression |
|Peripheral neuropathy |
|Carcinogen, mutagen |
|Mercurials ||Merbromin 2% (Mercurochrome) ||Antiseptic (obsolete) ||CNS ||Orogastric lavage, activated charcoal dimercaprol, succimer |
| (Chaps. 46 and 95) ||Thimerosal (Merthiolate) ||Kidney |
|Iodinated Compounds |
| Iodine || |
Tincture of iodine (2% iodine, 2% sodium iodide, and 50% ethanol)
Lugol solution (5% iodine)
|Antiseptic ||Caustic || |
Orogastric lavage Milk, starch, sodium thiosulfate
| Iodophors ||Povidone-iodine (Betadine) (0.01% iodine) ||Antiseptic ||Limited ||Same as iodine |
| Hydrogen peroxide ||H2O2 3%—household ||Disinfectant ||Oxygen emboli ||Orogastric lavage |
|H2O2 30%—industrial ||Caustic ||Radiographic evaluation |
| Potassium permanganate ||Crystals, solution ||Antiseptic ||Oxidizer, caustic, increased serum manganese || |
| Nonsubstituted ||Phenol ||Disinfectant || |
Decontamination: polyethylene glycol or water
| Substituted ||Hexachlorophene ||Disinfectant ||CNS effects ||Supportive |
|Quaternary Ammonium Compounds |
| Benzalkonium chloride ||Zephiran ||Disinfectant ||Caustic ||Endoscopy as needed |
The choice of disinfectant or sterilant depends on the degree of risk for infection involved in use of medical and surgical instruments and patient care items. Surgical instruments and cardiac and urinary catheters that enter the vascular system or other sterile tissues (so-called critical items) must be cleaned with a sterilant while instruments that contact mucous membranes or nonintact skin such as gastrointestinal (GI) endoscopes and laryngoscope blades (semicritical items) are cleaned with a high-level disinfectant such as ortho-phthalaldehyde or 7.5% hydrogen peroxide. Noncritical items such as bedpans, blood pressure cuffs, crutches, and computers are those that come in contact with intact skin but not mucous membranes and are cleaned with intermediate-level and low-level disinfectants such as bleach or phenol. Whether a chemical is classified as a sterilant or disinfectant depends on how it is used. Device sterilization with glutaraldehyde 3% requires a 10-hour cleaning cycle whereas high-level disinfection using the same chemical requires a 25-minute cleaning cycle.
The use of these xenobiotics evolved during the 20th century as their toxicity and the principles of microbiology became better understood. Two of the more toxic antiseptics—iodine and phenol—were gradually replaced by the less toxic iodophors and substituted phenols. The use of mercuric chloride was superseded by the organic mercurials such as merbromin and thimerosal, which also proved toxic. In recent years, newer xenobiotics, such as quaternary ammonium compounds, ethylene oxide, glutaraldehyde, and a peracetic acid–hydrogen peroxide mixture, are more extensively used.
This cationic biguanide has had extensive use as an antiseptic since the early 1950s. It is found in a variety of skin cleansers, usually as a 4% emulsion, and is also found in some mouthwash.
Few cases of deliberate ingestion of chlorhexidine are reported. Symptoms are usually mild, and GI irritation is the most likely effect after ingestion.25 Chlorhexidine has poor enteral absorption. In one case, ingestion of 150 mL of a 20% chlorhexidine gluconate solution resulted in oral cavity edema and significant irritant injury of the esophagus.130 In the same case, liver enzyme concentrations rose to 30 times normal on the fifth day after ingestion. Liver biopsy showed lobular necrosis and fatty degeneration. In another case, the ingestion of 30 mL of a 4% solution by an 89-year-old woman did not result in any GI injury.52 An 80-year-old woman with dementia ingested 200 mL of a 5% chlorhexidine solution and subsequently aspirated.79 She rapidly developed hypotension, respiratory distress, coma, and died 12 hours following ingestion.
Intravenous administration of chlorhexidine is associated with acute respiratory distress syndrome (ARDS)90 and hemolysis.28 Inhalation of vaporized chlorhexidine causes methemoglobinemia, likely as a consequence of the conversion of chlorhexidine to p-chloraniline.211 Methemoglobinemia due to this degradation product was also reported after the ingestion of a 0.5% chlorhexidine in 70% ethanol solution.107 This patient was successfully treated with methylene blue. In one patient, the rectal administration of 4% chlorhexidine resulted in acute colitis with ulcerations.68
Topical absorption of chlorhexidine is negligible. Contact dermatitis is reported in up to 8% of patients who received repetitive topical applications of chlorhexidine.69 More ominously, anaphylactic reactions, including shock, are associated with dermal application.7,148 Some of these cases of chlorhexidine-related anaphylaxis occurred during surgery, appearing 15 to 45 minutes after application of the antiseptic.13 Eye exposure results in corneal damage.205
Treatment guidelines for chlorhexidine exposure are similar to those for other potential caustics (Chap. 103). Patients with significant symptoms should undergo endoscopy, but the need for such extensive evaluation is uncommon.
Hydrogen peroxide, an oxidizer with weak antiseptic properties, has a long history of use as an antiseptic and a disinfectant.215 This oxidizer is generally available in 2 strengths: dilute, with a concentration of 3% to 9% by weight (usually 3%), sold for home use; and concentrated, with a concentration greater than 10%, used primarily for industrial purposes. Commercial-strength hydrogen peroxide is commonly found in solutions varying from 27.5% to 70%. Home uses for dilute hydrogen peroxide include cerumen removal, mouth gargle, vaginal douche, enema, and hair bleaching. Dilute hydrogen peroxide is also used as a veterinary emetic. Commercial uses of the more concentrated solutions include bleaching and cleansing textiles and wool, and producing foam rubber and rocket fuel. A 35% hydrogen peroxide solution is also available to the general public in health food stores and is sold as “hyperoxygenation therapy” and as an additive to oxygenate health food drinks.86 This potentially dangerous therapy is suggested as a treatment for a variety of conditions, including AIDS and cancer.
Toxicity from hydrogen peroxide occurs after ingestion, inhalation, injection, wound irrigation, rectal administration, dermal exposure, and ophthalmic exposure.215 Hydrogen peroxide has 2 main mechanisms of toxicity: local tissue injury and gas formation. The extent of local tissue injury and amount of gas formation are determined by the concentration of the hydrogen peroxide. Dilute hydrogen peroxide is an irritant, and concentrated hydrogen peroxide is a caustic. Gas formation results when hydrogen peroxide interacts with tissue catalase, liberating molecular oxygen, and water. At standard temperature and pressure, 1 mL of 3% hydrogen peroxide liberates 10 mL of oxygen, whereas 1 mL of the more concentrated 35% hydrogen peroxide liberates more than 100 mL of oxygen. Gas formation results in life-threatening embolization. The ingestion of “2 sips” of 33% hydrogen peroxide resulted in cerebral gas embolization and hemiplegia.173 Gas embolization is a result of dissection of gas under pressure into the tissues or of liberation of gas in the tissue or blood following absorption. The use of hydrogen peroxide in partially closed spaces, such as operative wounds, or its use under pressure during wound irrigation increases the likelihood of embolization.
Airway compromise manifested by stridor, drooling, apnea, and radiographic evidence of subepiglottic narrowing occurs.44 The combination of local tissue injury and gas formation from the ingestion of concentrated hydrogen peroxide causes abdominal bloating, abdominal pain, vomiting, and hematemesis.55,123 Endoscopy shows esophageal edema and erythema and significant gastric mucosal erosions.162,182
Symptoms consistent with sudden oxygen embolization include rapid deterioration in mental status, cyanosis, respiratory failure, seizures, ischemic ECG changes, and acute paraplegia.57,119 A 2-year-old boy died after ingesting 120 to 180 mL of 35% hydrogen peroxide.30 Antemortem chest radiography showed gas in the right ventricle, mediastinum, and portal venous system. Portal vein gas is also a prominent feature in other cases.55,85,155 Arterialization of oxygen gas embolization results in cerebral infarction.189 Encephalopathy with cortical visual impairment23 and bilateral hemispheric infarctions detected by MRI imaging occurred after ingestion of concentrated hydrogen peroxide.89 In a case of acute paraplegia after the ingestion of 50% hydrogen peroxide, MRI revealed discrete segmental embolic infarctions of the cervical and thoracic spinal cord as well as both cerebral hemispheres and left cerebellar hemisphere.119
Death from intravenous injection of 35% hydrogen peroxide is also reported.112 The application of a concentrated hydrogen peroxide solution to the scalp and hair as part of a hair highlighting procedure resulted in a severe scalp injury, including necrosis of the galea aponeurotica.183
Clinical sequelae from the ingestion of dilute hydrogen peroxide are usually much more benign.44,76 Nausea and vomiting are the most common symptoms.44 A whitish discoloration is noted in the oral cavity. Gastrointestinal injury is usually limited to superficial mucosal irritation, but multiple gastric and duodenal ulcers, accompanied by hematemesis, and diffuse hemorrhagic gastritis are reported.76,136 Portal venous gas embolization occurs as a result of the ingestion of 3% hydrogen peroxide.31,136,166
The use of 3% hydrogen peroxide for wound irrigation results in significant complications. Extensive subcutaneous emphysema occurred after a dog bite to a human’s face was irrigated under pressure with 60 mL of 3% hydrogen peroxide.192 Systemic oxygen embolism, causing hypotension, cardiac ischemia, and coma, resulted from the intraoperative irrigation of an infected herniorrhaphy wound.12 Gas embolism, resulting in intestinal gangrene, was reported to occur following colonic lavage with 1% hydrogen peroxide during surgical treatment of meconium ileus.187 Multiple cases of acute colitis are reported as a complication of administering 3% hydrogen peroxide enemas.132 The use of 3% hydrogen peroxide as a mouth rinse is associated with the development of oral ulcerations.170 Ophthalmic exposures result in conjunctival injection, burning pain, and blurry vision.44,131 Optic neuropathy including transient blindness (ability to visualize shadows only) and subsequent optic atrophy from possible inhalational of hydrogen peroxide is described.45 Cough, wheezing, and shortness of breath is associated with occupational exposure to peracetic acid–hydrogen peroxide mixtures used to clean endoscopic equipment.36
A careful examination should be performed to detect any evidence of gas formation. A chest radiograph is recommended to assess for gas in the cardiac chambers, mediastinum, or pleural space. Likewise, an abdominal radiograph is also recommended to assess for gas in the GI tract or portal system and define the extent of bowel distension. Magnetic resonance imaging and CT imaging are reasonable to detect brain and spinal cord lesions secondary to gas embolism and should be obtained if patient experiences neurologic effects.5,89,119 For those with clinical presentations consistent with esophageal, gastric or intestinal injury, endoscopic evaluation is recommended.162
The treatment of patients with hydrogen peroxide ingestions depends, to a large degree, on whether the patient has ingested a diluted or concentrated solution. Those with ingestions of concentrated solutions require expeditious evaluation. There is not enough evidence to support the dilution with milk or water. Nasogastric or orogastric aspiration of hydrogen peroxide is reasonable to consider if the patient presents immediately after ingestion. Induced emesis and activated charcoal are contraindicated. Gastric suctioning for patients with abdominal distension from gas formation is recommended. Place patients with clinical or radiographic evidence of gas in the heart in the Trendelenburg position to prevent gas from blocking the right ventricular outflow tract. Careful aspiration of intracardiac air through a central venous line is recommended in patients in extremis.30 Hyperbaric therapy is recommended in cases of life-threatening gas embolization after hydrogen peroxide ingestion.55,85,119,138,155,211 We recommend home observation for asymptomatic patients who unintentionally ingest small amounts of 3% hydrogen peroxide.
Iodine is one of the oldest topical antiseptics.184 Iodine usually refers to molecular iodine, also known as I2, free iodine, and elemental iodine, which is the active ingredient of iodine-based antiseptics. The use of ethanol as the solvent, such as in tincture of iodine, allows substantially more concentrated forms of I2 to be available. Iodine (I2) and tincture of iodine ingestions are much less common than in the past as a result of the change in antiseptic use from iodine to iodophor antiseptics.46
Iodophors have molecular iodine compounded to a high-molecular-weight carrier or to a solubilizing xenobiotic. Povidone-iodine, a commonly used iodophor, consists of iodine linked to polyvinylpyrrolidone (povidone). Iodophors, which limit the release of molecular iodine and are generally less toxic, are the current standard iodine-based antiseptic preparations. Iodophor preparations are formulated as solutions, ointments, foams, surgical scrubs, wound-packing gauze, and vaginal preparations. The most common preparation is a 10% povidone-iodine solution that contains 1% “available” iodine (referring to all oxidizing iodine species), but only 0.001% free iodine (referring only to molecular iodine).18,69
Iodine is used to disinfect medical equipment and drinking water. Iodine is effective against bacteria, viruses, protozoa, and fungi, and is used both prophylactically and therapeutically.42 Iodine is cytotoxic and also an oxidant. It is thought to work by binding amino and heterocyclic nitrogen groups, oxidizing sulfhydryl groups, and saturating double bonds. Iodine also iodinates tyrosine groups.69 It appears to induce apoptosis through oxidative stress.95
Significant systemic absorption of iodine from topical iodine or iodophor preparations is rare.157 Markedly elevated iodine concentrations occur in patients who receive topical iodophor treatments to areas of dermal breakdown, such as burn injuries.109 Significant absorption occurs when iodophors are applied to the vagina, perianal fistulas, umbilical cords, and the skin of low-birth-weight neonates.212 The mucosal application of povidone-iodine during a hysteroscopy procedure resulted in acute kidney injury (AKI) that transiently required hemodialysis.14 A fatality following intraoperative irrigation of a hip wound with povidone-iodine was also reported.37 In this latter case, the postmortem serum iodine concentration was 7,000 mcg/dL (normal: 5–8 mcg/dL).
Problems associated with the use of iodine include unpleasant odor, skin irritation, allergic reactions, and clothes staining. Ingestion of iodine causes abdominal pain, vomiting, diarrhea, GI bleeding, delirium, hypovolemia, anuria, and circulatory collapse. Severe caustic injury of the GI tract occurs. The ingestion of approximately 45 mL of a 10% iodine solution resulted in death from multisystem failure 67 hours after ingestion.48 In another case, the ingestion of 200 mL of tincture of iodine containing 60 mg/mL iodine and 40 mg/mL potassium iodide in 70% v/v ethanol resulted in AKI and severe hemolysis.126
Reports of adverse consequences from iodophor ingestions are rare. In one case report, a 9-week-old infant died within 3 hours of receiving povidone-iodine by mouth.106 In this unusual case, the child was administered 15 mL of povidone-iodine mixed with 135 mL of polyethylene glycol by nasogastric tube over a 3-hour period for the treatment of infantile colic. Postmortem examination showed an ulcerated and necrotic intestinal tract. A blood iodine concentration of 14,600 mcg/dL was recorded. Significant toxicity from intentional ingestions of iodophors in adults is not documented.
Acid–base disturbances are among the most significant abnormalities associated with iodine and iodophors. Metabolic acidosis occurred in several burn patients after receiving multiple applications of povidone-iodine ointment.109,158 These patients had elevated serum iodine concentrations and normal lactate concentrations. The exact etiology of the acidosis remains unclear. Postulated mechanisms for the acidosis include the povidone-iodine itself (pH 2.43), bicarbonate consumption from the conversions of I2 to NaI, and decreased renal elimination of H+ as a consequence of iodine toxicity.158 Metabolic acidosis associated with an elevated lactate concentration after iodine ingestion likely reflects tissue destruction.42
Electrolyte abnormalities also occur following the absorption of iodine. A patient with decubitus ulcers who received prolonged wound care with povidone-iodine–soaked gauze developed hypernatremia, hyperchloremia, metabolic acidosis, and AKI.37 The hyperchloremia was thought to be caused by a spurious elevation of measured chloride ions as a consequence of the interference of iodine with the chloride assay. This interference occurs on the Technicon STAT/ION autoanalyzer, but does not occur when the silver halide precipitation assay is used.42 Spurious hyperchloremia from iodine (or iodide) results in the calculation of a low or negative anion gap (Chaps. 7 and 12).24,54 The spurious effect of iodide on chloride and anion gap occurs even with very low serum iodide concentrations (<1 mEq/L) and the degree of anion gap deviation does not reliably predict the amount of iodide present.105
Other problems associated with topical absorption of iodine-containing preparations are hypothyroidism (particularly in neonates),24,193 hyperthyroidism,169,174 elevated liver enzyme concentrations, neutropenia, anaphylaxis,1 and hypoxemia.42 Because of the lack of consistency between iodine concentrations and clinical manifestations, and because many of these patients had significant secondary medical problems that contributed to their symptoms, the exact relationship between iodine absorption and the development of a specific clinical syndrome remains speculative. However, a clinical controlled trial that compared preterm infants exposed to either topical iodinated antiseptics or to chlorhexidine-containing antiseptics showed that the infants exposed to topical iodine-containing antiseptics were more likely to have higher TSH concentrations and elevated urine iodine concentrations than were those in the chlorhexidine group.116
Contact dermatitis can result from repetitive applications of iodophors.127 A dermal burn results from the trapping of an iodophor solution under the body of a patient in a pooled dependent position or under a tourniquet.118,142 Aspiration pneumonitis is rarely described following the intraoperative application of povidone-iodine prior to craniofacial surgeries.27 These patients generally recover with supportive care.
The patient who ingests iodine requires expeditious evaluation, stabilization, and decontamination. If signs of perforation are absent, it is reasonable to proceed with careful nasogastric or orogastric aspiration and lavage to limit the caustic effect of the iodine. In symptomatic patients, irrigation with a starch solution is recommended to convert iodine to the much less toxic iodide and, in the process, turn the gastric effluent dark blue-purple. This change in color is a useful guide in determining when lavage can be terminated. If starch is not available, milk or 100 mL of a solution of 1% to 3% sodium thiosulfate is a reasonable alternative to convert any remaining iodine to iodide. We recommend early endoscopy in patients with significant symptoms to help assess the extent of the GI injury. Hemodialysis and continuous venovenous hemodiafiltration were used successfully to enhance elimination of iodine in a patient with CKD with iodine toxicity who developed renal deterioration after undergoing continuous mediastinal irrigation with povidone-iodine.99 The benefit of hemodialysis or continuous venovenous hemodiafiltration is unknown in patients with normal kidney function and therefore not routinely recommended at this time.
Most patients with iodophor ingestion require only supportive management. The use of starch or sodium thiosulfate is reasonable in symptomatic patients.
Potassium permanganate (KMnO4) is a violet water-soluble xenobiotic that is usually sold as crystals or tablets or as a 0.01% dilute solution.96 Historically, it was used as an abortifacient, urethral irrigant, lavage fluid for alkaloid poisoning, and snakebite remedy. Currently, potassium permanganate is most often used in baths and wet bandages as a dermal antiseptic, particularly for patients with eczema.
Potassium permanganate is a strong oxidizer, and poisoning results in local and systemic toxicity.195 Upon contact with mucous membranes, potassium permanganate reacts with water to form manganese dioxide, potassium hydroxide, and molecular oxygen. Local tissue injury is the result of contact with the nascent oxygen, as well as the caustic effect of potassium hydroxide. A brown-black staining of the tissues occurs from the manganese dioxide. Systemic toxicity occurs from free radicals generated by absorbed permanganate ions.221
Dermal contact leads to cutaneous staining. Following ingestion, initial symptoms include nausea and vomiting. Laryngeal edema and ulceration of the mouth, esophagus, and, to a lesser extent, the stomach, result from the caustic effects. Airway obstruction and fatal GI perforation and hemorrhage are reported.43,133,150 Esophageal strictures and pyloric stenosis are potential late complications.103
Although potassium permanganate is not well absorbed from the GI tract, systemic absorption occurs, resulting in life-threatening toxicity. Systemic effects include hepatotoxicity, AKI, methemoglobinemia, hemolysis, hemorrhagic pancreatitis, airway obstruction, ARDS, disseminated intravascular coagulation, and cardiovascular collapse.114,125,133,150 Elevation in blood and serum manganese concentrations also occurs, confirming systemic absorption.
Chronic ingestion of potassium permanganate results in classic manganese poisoning (manganism) characterized by behavioral changes, hallucinations, and delayed onset of parkinsonian-like symptoms. A 66-year-old man who ingested 10 g of potassium permanganate instead of potassium iodate over a 4-week period (because of medication mislabeling) developed impaired concentration and autonomic and visual symptoms. He also developed abdominal pain, gastric ulceration, and alopecia. Serum manganese concentration was elevated. Nine months later, the patient had extrapyramidal signs consistent with parkinsonism (Chap. 94).83
Because the consequential effects of potassium permanganate ingestion are a result of the liberation of strong alkalis, immediate assessment for evidence of airway compromise should be performed in such a patient. Dilution with milk or water is reasonable. Patients with symptoms consistent with caustic injury should undergo early upper–GI tract endoscopy.96 Corticosteroids are recommended if laryngeal edema is present. When systemic toxicity is suspected, of liver enzymes, blood urea nitrogen, creatinine, lipase, serum manganese, and methemoglobin concentrations all will help in the evaluation. We recommend methylene blue for clinically significant methemoglobinemia (Antidotes in Depth: A43). Dermal irrigation with dilute oxalic acid removes cutaneous staining.195 The administration of N-acetylcysteine (Antidotes in Depth: A3) to increase reduced glutathione production, thereby limiting free radical–mediated oxidative injury in cases of systemic potassium permanganate poisoning, is suggested, but there is inadequate evidence to support routine use at this time.221
Ethanol and isopropanol (Chaps. 76 and 106) are commonly used as skin antiseptics. When sold as rubbing alcohol, the standard concentration for these solutions is usually 70%. In recent years, alcohol-based hand sanitizers containing 60% to 95% ethyl or isopropyl alcohol have become ubiquitous throughout patient care units, jails, and some public buildings as a primary infection control measure. Their antiseptic action is a result of their ability to coagulate proteins. Isopropanol is slightly more germicidal than ethanol.69 The alcohols have limited efficacy against viruses or spores. Isopropanol tends to be more irritating than ethanol and causes more pronounced central nervous system depression.213 Unfortunately, readily available alcohol-based sanitizers are a tempting source for patients admitted with alcohol abuse disorders.51,217 In one report, a patient was admitted to the hospital with chest pain. While in the hospital the patient became hypotensive and delirious. He was later found in the bathroom drinking an alcohol-based hand wash that contained 63% isopropanol.51 The clinical effects and treatment for alcohol poisoning are discussed in Chaps. 76 and 106.
Chlorine, one of the first antiseptics, is still used in the treatment of the community water supply and in swimming pools. Chlorine is a potent pulmonary irritant that can cause severe bronchospasm and ARDS. Chapter 121 contains a further discussion of chlorine.
Sodium hypochlorite (NaClO), found in household bleaches and in Dakin solution, remains a commonly used disinfectant. First used in the late 1700s to bleach clothes, its usefulness arises from its oxidizing capability, measured as “available chlorine,” and its ability to release hypochlorous acid (HClO) slowly. It is used to clean blood spills and to sterilize certain medical instruments. A 0.5% hypochlorite solution is sometimes recommended for dermal and soft-tissue wound decontamination after exposure to biologic and chemical warfare agents (Chaps. 126 and 127).86 Toxicity from hypochlorite is mainly a result of its irritant effects. The ingestion of large amounts of household liquid bleach (5% sodium hypochlorite) on rare occasions can result in esophageal burns with subsequent stricture formation.56 In a cat model of bleach ingestion, a high incidence of mucosal injury and stricture formation was noted.216 However, the vast majority of household bleach ingestions in humans do not cause significant GI injuries.159 Accordingly, we recommend not performing routine endoscopic evaluation when assessing asymptomatic patients with household liquid bleach ingestions. Endoscopy is reasonable in symptomatic patients. Endoscopy is recommended in symptomatic patients who ingest a more concentrated “industrial strength” bleach preparation such as 35% sodium hypochlorite, because of the increased likelihood of local tissue injury (Chap. 103).
Both inorganic mercurials, such as mercuric bichloride (HgCl2), and organic mercurials, such as merbromin (C20H8Br2HgNa2O6) (mercurochrome) and thimerosal (C9H9HgNaO2S) (merthiolate), which both contain 49% mercury, were previously used as topical antiseptics. The usefulness of mercurials is significantly limited because of their relatively weak bacteriostatic properties and the many concerns associated with mercury toxicity (Chap. 95). Repeated application of topical mercurial causes significant absorption and systemic toxicity.139,176 The use of high-dose hepatitis B immunoglobulin (HBIG) causes mercury toxicity because of the use of thimerosal as a preservative in the HBIG preparation.121 In one case, a 44-year-old man received 250 mL of HBIG (containing about 30 mg of thimerosal) over 9 days following liver transplantation.121 He developed speech difficulties, tremor, and chorea. His whole blood mercury concentration was 104 mcg/L (normal <10 mcg/L).
Formaldehyde is a water-soluble, highly reactive gas at room temperature. Formalin consists of an aqueous solution of formaldehyde, usually containing approximately 37% formaldehyde and 12% to 15% methanol. Formaldehyde is irritating to the upper airways, and its odor is readily detectable at low concentrations. Lethality in adults follows ingestion of as little as 30 to 60 mL of formalin.49
Formerly used as a disinfectant and fumigant, its role as a disinfectant is now largely confined to the maintenance of hemodialysis machines. Nonetheless, formaldehyde has many other applications. Formaldehyde is widely used in construction including wood processing and the manufacturing of furniture, textiles, and carpeting.101 Health care workers are probably most familiar with the use of formaldehyde as a tissue fixative and embalming agent. Medical students are routinely exposed to formalin in the anatomy laboratory.167
Exposure to formaldehyde, a potent tissue fixative results in both local and systemic symptoms, causing coagulation necrosis, protein precipitation, and tissue fixation. Ingestions of formalin results in significant gastric injury, including hemorrhage, diffuse necrosis, perforation, and stricture.3,11 The most extensive damage appears in the stomach, with only occasional involvement of the small intestine and colon.220 Chemical fixation of the stomach occurs. Esophageal involvement is not very prominent and, if present, is usually limited to its distal segment.
The most striking and rapid systemic manifestation of formaldehyde poisoning is anion gap metabolic acidosis, resulting both from tissue injury and from the conversion of formaldehyde to formic acid. Although the methanol component of the formalin solution is readily absorbed and produces methanol concentrations reportedly as high as 40 mg/dL,22,49 the rapid metabolism of formaldehyde to formic acid is responsible for much of the metabolic acidosis (Chap. 106).
Patients presenting after formalin ingestions complain of the rapid onset of severe abdominal pain, vomiting, and diarrhea. Altered mental status and coma usually follow rapidly. Physical examination demonstrates epigastric tenderness, hematemesis, cyanosis, hypotension, and tachypnea. Profound hypotension is due to decreased myocardial contractility, as well as hypovolemic shock.78,203 Early endoscopic findings include ulceration, necrosis, perforation, and hemorrhage of the stomach, with infrequent esophageal involvement. Chemical pneumonitis occurs after significant inhalational exposure.161 Intravascular hemolysis is described in hemodialysis patients whose dialysis equipment contained residual formaldehyde after undergoing routine cleaning.152,165
Occupational and environmental exposure to formaldehyde receives considerable attention. In particular, there is concern over the potential off-gassing of formaldehyde from the widely used urea formaldehyde building insulation and particle board.149 Headache, nausea, skin rash, sore throat, nasal congestion, and eye irritation are associated with the use of these polymers.39 Formaldehyde, at concentrations as low as 1 ppm, causes significant irritation to mucous membranes of the upper respiratory tract and conjunctivae.82,120 Formaldehyde is also a potential sensitizer for immune-mediated reversible bronchospasm.75 The exact immunologic mechanism is not yet elucidated, although it is likely that formaldehyde acts as a hapten. In addition, formaldehyde is a dermal sensitizer.194
Concerns about the health effects from the off-gassing of formaldehyde in trailers used by the Federal Emergency Management Agency (FEMA) after Hurricane Katrina illustrates the potential public health issues related to low-level formaldehyde exposure.124 A Centers for Disease Control and Prevention (CDC) investigation revealed that air formaldehyde concentrations in closed, unventilated trailers are, in fact, high enough to cause acute symptoms in some people.4 Long-term effects after these exposures remain undefined.
Formaldehyde exposure is associated with an increased incidence of nasopharyngeal carcinoma.2,71,156,177 Although its role in the pathogenesis of cancer in humans is the subject of much debate,33,128 formaldehyde is classified as a Group 1, known, carcinogen by the International Agency for Research on Cancer (IARC).
Dilution with water is reasonable for the immediate management of a patient who has ingested formalin. Gastric aspiration with a small-bore nasogastric or orogastric tube is also reasonable to limit systemic absorption. Activated charcoal should not be used. Significant acidemia is treated with sodium bicarbonate and folinic acid (Chap. 106). Immediate hemodialysis removes the accumulating formic acid as well as the parent molecules formaldehyde and methanol and is reasonable in refractory acidemia (Antidotes in Depth: A33 and A34).6,49 Early endoscopy is recommended for all patients with significant GI manifestations to assess the degree of burn injury. Surgical intervention is required for those with suspected severe burns, tissue necrosis and/or perforation.220 Emergent gastrectomy, as well as late surgical intervention to relieve formaldehyde-induced gastric outlet obstruction, is rarely required.72,104
Phenol is one of the oldest antiseptics. It is rarely used as an antiseptic today, because of its toxicity, and is replaced by the many phenolic derivatives. Currently, phenol is used as a disinfectant and chemical intermediary. The concentration of phenol in consumer products can vary significantly, from 0.1% to 4.7% in various lotions, ointments, gels, gargles, lozenges, and throat sprays and up to 89% in nail cauterizer solution.69 Although many cases of phenol poisoning were reported in the past, acute oral overdoses of phenol-containing solutions are uncommon today.62
Phenol acts as a caustic causing cell wall disruption, protein denaturation, and coagulation necrosis. It also acts as a central nervous system (CNS) stimulant. Intentional ingestion of concentrated phenol, ingestion of phenol-containing water, occupational exposure to aerosolized phenol, dermal contact, and parenteral administration result in symptomatic phenol poisoning. Phenol demonstrates excellent skin penetrance and causes severe dermal burns, resulting in potentially fatal systemic toxicity within minutes to hours.16,113 Deaths from parenteral administration of phenol are reported. The lethal oral dose is as little as 1 g.84
Clinical manifestations can be divided into local and systemic symptoms. Systemic symptoms from GI or dermal absorption of phenol are usually more dangerous than the local effects. Manifestations of systemic toxicity include CNS and cardiac manifestations. Central nervous system effects include central stimulation, seizures, lethargy, and coma.65 In a study of patients who had ingested Creolin (26% phenol), CNS toxicity predominated.196 Of the 52 patients who were evaluated at the hospital, 9 developed lethargy and 2 developed coma. Seizures were not reported. Cardiac signs and symptoms from phenol include tachycardia, bradycardia, and hypotension.65 Parenteral absorption of 10 mL concentrated 89% phenol resulted in hypoxemia, ARDS, pulmonary nodular opacities, and AKI requiring intubation and hemodialysis.64 This last case was associated with a phenol concentration of 87 mg/dL (normal <2 mg/dL).
Other systemic effects include hypothermia, metabolic acidosis, methemoglobinemia, and rabbit syndrome.84,97 Rabbit syndrome is most commonly observed as a distinctive extrapyramidal effect from antipsychotics and is characterized by fine rapid repetitive movements of the perioral musculature resembling a rabbit’s chewing movements. Increased acetylcholine release and a relative dopaminergic hypofunction explain the development of rabbit syndrome after phenol exposure.97
Local toxicity to the GI tract from the ingestion of phenol results in nausea, painful oral lesions, vomiting, severe abdominal pain, bloody diarrhea, and dark urine.8,94 Serious GI burns are uncommon, and strictures are rare. White patches in the oral cavity occur. In the Creolin study cited above, only 1 of 17 patients who underwent endoscopy had a significant esophageal burn.196 Dermal exposures to phenol usually result in a light-brown staining of the skin. Excessive dermal absorption of phenol during chemical peeling procedures is associated with dysrhythmias and many of the other toxic manifestations.208,214
Markedly elevated blood and urine concentrations of phenol are detected after ingestion, or dermal absorption, of phenol and phenol-containing compounds.16,84
When phenol is mixed with water, a bilayer with unique properties is created that makes it difficult to remove from tissues. A variety of treatments are suggested for dermal and gastric decontamination of phenol. A study using a rat model showed that cutaneous decontamination with a low-molecular-weight polyethylene glycol solution decreased mortality, systemic effects, and dermal burns.21 Although this study suggested that polyethylene glycol (PEG) was superior to water as a decontamination, a subsequent study using a swine model could not demonstrate a difference between these 2 therapies.164 In another swine model, PEG 400 and 70% isopropanol were both superior to water washes and equally effective in decreasing dermal burn.135 Given the lack of definitive efficacy data, either low-molecular-weight PEG, for example, PEG 300 or 400 (not to be confused with high-molecular-weight PEG that is used for whole-bowel irrigation), or high-flow water are reasonable for dermal irrigation and careful gastric decontamination. Endoscopic evaluation, for symptomatic patients to determine the extent of GI injury is recommended.
Substituted Phenols and Other Related Compounds
Hexachlorophene, a trichlorinated bis-phenol, is considered generally less tissue-toxic than phenol. During the 1970s, an association was observed between repetitive whole-body washing of premature infants with 3% hexachlorophene and the development of vacuolar encephalopathy and cerebral edema.129 There are also multiple reports of significant neurologic toxicity and death in children who became toxic after ingesting hexachlorophene.77 In addition, fatalities also occurred after patients absorbed substantial amounts of hexachlorophene during the treatment of burns.29 The use of hexachlorophene has declined significantly. Currently used substituted phenols include a sodium solution of octylphenoxyethoxyethyl ether sulfonate, chloroxylenol and cresol.
A sodium solution of octylphenoxyethoxyethyl ether sulfonate and lanolin is a safe antiseptic. Irritative effects such as nausea, vomiting, and diarrhea are the main adverse effects following ingestion.
In a study of poisoning admissions to Hong Kong hospitals, the ingestion of a household disinfectant that contained 4.8% chloroxylenol, 9% pine oil, and 12% isopropanol accounted for 10% of admissions.26 Aspiration (perhaps, in part, because of the pine oil) occurred in 8% of these patients, resulting in upper airway obstruction, pneumonia, and ARDS. More common symptoms included nausea, vomiting, sore mouth, sore throat, drowsiness, abdominal pain, and fever. Dermal contact with Dettol results in full-thickness chemical burns.40
Cresol, a mixture of 3 isomers of methylphenol, has better antiseptic activity than phenol and is a commonly used disinfectant. Exposure to concentrated cresol results in significant local tissue injury, hemolysis, AKI, hepatic injury, and CNS and respiratory depression.40,70,98,219 Phenol concentrations, as well as cresol concentrations, serve as markers of exposure.219
Treatment is supportive care emphasizing decontamination.
Quaternary Ammonium Compounds
Quaternary ammonium compounds, positively charged compounds where 4 organic groups are linked to a nitrogen atom (NR4+), are cationic surfactants (surface-active agent) that are used as disinfectants, detergents, and sanitizers. Chemically, the quaternary ammonium compounds are synthetic derivatives of ammonium chloride, and structurally similar to other quaternary ammonium derivatives, such as carbamate cholinesterase inhibitors and neuromuscular blockers. Other cationic surfactants include the pyridinium compounds and the quinolinium compounds. Benzalkonium chloride was one of the most commonly employed quaternary ammonium compounds in the past. Many newer quaternary ammonium compounds have supplanted its use. However, nebulized solutions used for the treatment of asthma, including albuterol and ipratropium bromide, contain small amounts of benzalkonium chloride.
Quaternary ammonium compounds are usually less toxic than phenol or formaldehyde. Most of the infrequent complications that are described result from ingestions of benzalkonium chloride. Complications of these ingestions include burns to the mouth and esophagus, CNS depression, elevated liver enzyme concentrations, metabolic acidosis, and hypotension.80,147,210 Paralysis is also occasionally described as a complication of these ingestions and is presumably a result of cholinesterase inhibition at the neuromuscular junction.62 Chronic inhalational exposure is associated with occupational asthma.17 Topical use of the quaternary ammonium compounds causes contact dermatitis.190 Ingestion of a 2.25% ammonium chloride solution, marketed as a bacteriostatic for algae and odor humidifier treatment, results in serious GI and pulmonary injury.67
Ingestions of other cationic surfactants, such as the pyridinium-derived cetrimonium bromide are associated with corrosive burns to the mouth, lips, and tongue.137 Peritoneal irrigation with cetrimonium bromide produces metabolic abnormalities, hypotension, and methemoglobinemia.9,134 Intravenous administration of cetrimonium bromide leads to hemolysis, muscle paralysis, and cardiac arrest.58
Treatment recommendations following the ingestion of the quaternary ammonium compounds and other cationic surfactants are similar to those for other potentially caustic ingestions. Emergency department evaluation is recommended for all patients who ingest more than a taste of a dilute (<1%) solution. Therapy is mainly supportive care. Endoscopy is indicated if signs and symptoms suggest the possibility of a burn.
Ethylene oxide (C2H4O) is a gas that is commonly used to sterilize heat-sensitive material in health care facilities. Unlike antiseptics and disinfectants, which generally do not exhibit full sporicidal activity, sterilants, such as ethylene oxide, inactivate all organisms. Ethylene oxide is also used in the synthesis of many chemicals, including ethylene glycol, surfactants, rocket propellants, and petroleum demulsifiers, and is used as a fumigant. Ethylene oxide has a cyclic ester structure that acts as an alkylating agent, reacting with most cellular components, including DNA and RNA.
Medical attention regarding ethylene oxide toxicity has centered on its mutagenic and possible carcinogenic effects.108 Approximately 270,000 workers (including 96,000 hospital workers) in the United States are at risk for occupational exposure to ethylene oxide.199 Retrospective studies suggest a possible excess incidence of leukemia and gastric cancer in ethylene oxide exposed workers.81,199 The 2008 IARC updated monographs concluded that there was limited evidence for carcinogenicity in humans, with an association with lymphatic, hematopoietic, and breast cancers. However, sufficient evidence for the carcinogenicity of ethylene oxide was found in experimental animals. Evidence suggests direct-acting alkylating effects leading to genotoxicity. Ethylene oxide was subsequently placed in IARC group I—carcinogenic to humans.87 An increased incidence of spontaneous abortions is associated with occupational exposure to ethylene oxide.74
The acute toxicity of ethylene oxide is mainly the result of its irritant effects, including conjunctival, upper respiratory tract, GI, and dermal irritation. Dermal burns from acute exposure to ethylene oxide are reported. Acute exposure to a broken ethylene oxide ampule (17 g) by a 43-year-old recovery room nurse resulted in nausea, lightheadedness, malaise, syncope, and recurrent seizures.181 There were no long-term complications. In another case of acute exposure, coma was followed by an irreversible parkinsonism.10
Chronic exposure to high concentrations of ethylene oxide causes mild cognitive impairment and motor and sensory neuropathies.20,63,146 Hazard studies of occupational exposure have demonstrated no increased incidence of cancer in exposed populations over the expected occurrence rate.32,198,204
Treatment for patients with ethylene oxide exposure is supportive.
Glutaraldehyde is a liquid solution used in the cold sterilization of nonautoclavable endoscopic, surgical, and dental equipment. It is also employed as a tissue fixative, embalming fluid, preservative, and tanning agent, in radiographic solutions, and in the treatment of warts.60 Glutaraldehyde (C5H8O2) is a dialdehyde with 2 active carbonyl groups that is less volatile than formaldehyde. It kills all microorganisms, including viruses and spores. The sterilant ability of glutaraldehyde results from the alkylation of sulfhydryl, hydroxyl, carboxyl, and amino groups, within microbes interfering with RNA, DNA, and protein synthesis.179 It is prepared as a 2% alkaline solution in 70% isopropanol. Health care workers are exposed to glutaraldehyde vapors when equipment is processed in poorly ventilated areas, or in open immersion baths or after spills. Under these circumstances, the evaporation of glutaraldehyde results in the increase in ambient air concentrations that exceeds recommended limits. Approximately 35,000 workers are occupationally exposed to glutaraldehyde annually.160 To prevent exposure, OSHA recommends the use of personal protective equipment with elbow-length gloves of butyl rubber or nitrile, gowns and eye protection. Local exhaust ventilation at the point of release should include either a local exhaust hood or ductless hood. Enclosed processing is also recommended when available. Respirators should be available in the event that ventilation fails for any reason.153 Patients are exposed when diagnostic instruments are inadequately rinsed following cold sterilization with glutaraldehyde.
Clinical signs and symptoms are comparable to those of formaldehyde exposure, although human toxicity data are limited. Animal studies show that the inhalational and dermal toxicity of glutaraldehyde are similar to those of formaldehyde at equivalent doses.202
Glutaraldehyde is a mucosal irritant. Coryza, epistaxis, headache, asthma, chest tightness, palpitations, tachycardia, and nausea are all associated with glutaraldehyde vapor exposure.15,34,143,154 Occupational asthma, contact dermatitis, and ocular inflammation also occur.38,151,186 Colitis is reported following the use of endoscopes contaminated with residual glutaraldehyde solution.188 Patients with glutaraldehyde-induced colitis typically present with fever, chills, severe abdominal pain, bloody diarrhea, and an elevated white blood cell count within 48 hours after colonoscopy or sigmoidoscopy.
The IARC has not ranked the carcinogenic potential of glutaraldehyde.
Treatment recommendations are similar to those for patients with formaldehyde exposure. Prompt removal from the exposure is essential. Copious irrigation with water is recommended for dermal decontamination. Severe inhalational exposures require hospital admission for observation, supportive care, and treatment of bronchospasm.
In recent years, some hospitals have started using ortho-phthalaldehyde (OPA) or a mixture of hydrogen peroxide and peracetic acid as alternatives to glutaraldehyde for high-level disinfection.172 These alternative disinfectants do not appear to have the pulmonary or dermal sensitizing properties associated with glutaraldehyde, although they do cause some irritation to skin and mucous membranes.172 A single case of occupational asthma related to OPA exposure was reported in 2014, proven with a specific inhalation challenge, and represents the only reported case in the literature.175 Oropharyngeal and laryngeal burns are also reported in a patient exposed to residual OPA during transesophageal echocardiography.185
Boric acid is an odorless, transparent crystal, although it is most commonly available as a finely ground white powder. It is also available as a 2.5% to 5% aqueous solution. Boric acid (H3BO3), prepared from borax (sodium borate; Na2B4O7⋅10 H2O), was first used as an antiseptic by Lister in the late 19th century. Although used extensively over the years for antisepsis and irrigation, boric acid is only weakly bacteriostatic. As a result of its germicidal limitations and its inherent toxicity, boric acid is nearly obsolete in modern antiseptic therapy. Nonetheless, it continues to be used as an antimicrobial to treat such conditions as vulvovaginal candidiasis.88,100,163 Boric acid is also employed in the treatment of cockroach infestation and as a soap, contact lens solution, toothpaste, and food preservative.66 Recently, do-it-yourself recipes for children’s slime, a squishy colorful play material, include boric acid as a major ingredient.47
Boric acid is readily absorbed through the GI tract, wounds, abraded skin, and serous cavities. Absorption does not occur through intact skin. Boric acid is predominantly eliminated unchanged by the kidney. Small amounts are also excreted into sweat, saliva, and feces.59 Boric acid is concentrated in the brain and liver.
The exact mechanism of action of toxicity remains unclear. Although it is an inorganic acid, it is not a caustic. Local effects are limited to tissue irritation.
Over the years, boric acid developed a reputation as an exceptionally potent toxin. This reputation derived in great part from a series of reports involving neonatal exposures to boric acid resulting in high morbidity and mortality. Life-threatening toxicity resulted from the repetitive topical application of boric acid for the treatment of diaper rash or the use of infant formulas unintentionally contaminated with boric acid.59,218 Fatality rates greater than 50% were reported in some series.218 Although infants appear to be the most sensitive to the toxic effects of boric acid, many cases of significant toxicity are also reported in adults. These cases date predominantly from the first half of the 20th century when boric acid was widely used as an irrigant. Routes of exposure to boric acid, resulting in fatalities, include wound irrigation, pleural irrigation, rectal washing, bladder irrigation, and vaginal packing.209
Boric acid poisoning usually involves multiple exposures over a period of days. Gastrointestinal, dermal, CNS, and renal manifestations predominate. The initial effects—nausea, vomiting, diarrhea, and occasionally crampy abdominal pain—are frequently confused with an acute gastroenteritis. At times, the emesis and diarrhea are greenish blue.218 Following the onset of GI signs and symptoms, the majority of patients develop a characteristic intense generalized erythroderma.218 This rash, described as producing a “boiled lobster” appearance, appears indistinguishable from toxic epidermal necrolysis or staphylococcal scalded skin syndrome in the neonate.122,178 The rash is especially noticeable on the palms, soles, and buttocks.59 Typically, extensive desquamation takes place within 1 to 2 days. On occasion, prominent mucous membrane involvement of the oral cavity and conjunctivae is also apparent.218 At the time of development of the erythroderma, patients, particularly young infants, develop prominent signs of CNS irritability, resembling meningeal irritation. Seizures, delirium, and coma occur.59 Acute kidney injury is common, both as a result of the renal elimination of this compound and prerenal azotemia from GI losses.59 Other complications of boric acid poisoning include hepatic injury, hyperthermia, and cardiovascular collapse. A marked decrease in the incidence of significant boric acid poisoning is attributed to the abandonment of boric acid as an irrigant and particularly its removal from the nursery setting.
Two retrospective studies on boric acid ingestions suggest that a single acute ingestion of boric acid is generally quite benign.115,117 In these studies, 79% to 88% of patients remained asymptomatic. Symptoms, when present, primarily consist of nausea and vomiting. None of the 1,184 patients in these 2 studies manifested the generalized erythroderma so commonly described in previous reports. Central nervous system manifestations of acute overdose were infrequent and limited to occasional lethargy and headache. Kidney injury did not occur following single acute ingestions.
Fatalities from massive acute ingestion of boric acid are reported in both unintentional ingestions in children and intentional ingestions in adults.66,171 Fatality resulted from a single ingestion of 2 cups (280 g) of boric acid crystals dissolved in water by a 45-year-old man. Signs and symptoms on presentation (2 days after ingestion) included nausea, vomiting, green diarrhea, lethargy, hypotension, AKI, and a prominent “boiled lobster” rash on his trunk and extremities. In another case, the ingestion of 30 g of boric acid by a 77-year-old man resulted in similar symptoms and death 63 hours postingestion, despite hemodialysis.91
Long-term chronic exposure to boric acid results in alopecia in adults and seizures in children.145 A 32-year-old woman who over a 7-month period ingested commercial mouthwash products containing boric acid developed progressive hair loss.201 The chronic application of a commercial preparation of borax and honey mixture to pacifiers resulted in the development of recurrent seizures in 9 infants, which resolved after the mixture was withheld.61,145
Treatment of boric acid toxicity is supportive care. Activated charcoal is not recommended because of its relatively poor adsorptive capacity for boric acid.41 Because boric acid has a low molecular weight and relatively small volume of distribution, in cases of massive oral overdose or AKI, hemodialysis, or perhaps exchange transfusion in infants, is reasonable in shortening the half-life of boric acid.35,117,141,206 Although forced diuresis is suggested by others to enhance renal elimination, this is highly unlikely to be successful and is not recommended.207
Sodium chlorate is a strong oxidizer. At one time, the chlorate salts sodium chlorate and potassium chlorate were used as medicinals to treat inflammatory and ulcerative lesions of the oral cavity and could be found in various mouthwash, toothpaste, and gargle preparations.197 Although their use as local antiseptics is obsolete, chlorates are used as herbicides and in the manufacture of matches, explosives, and dyestuffs.92 Historically, cases have included dispensing errors that confused sodium chlorate with sodium sulfate or sodium chloride.92 Sodium chlorate in the form of white crystals was mistaken for table sugar in one case.73 A case of significant toxicity from the inhalation of atomized chlorates is also reported.92 More recent cases of chlorate poisoning continue to result from the ingestion of sodium chlorate–containing weed killers168,197 and industrial chemicals.111
Sodium chlorate is rapidly absorbed from the GI tract and eliminated predominantly unchanged from the kidneys.93 Its systemic effects are chiefly hematologic and renal. The major mechanism of toxicity of chlorate is its ability to oxidize hemoglobin and increase red blood cell membrane rigidity.191 Consequently, significant methemoglobinemia and hemolysis result. Methemoglobinemia occurs prior to or after the development of hemolysis.144,200 The hemolysis and the resultant hemoglobinuria secondarily causes disseminated intravascular coagulation and potential renal toxicity. Chlorates are also directly toxic to the proximal renal tubule.110 The worsening kidney function is especially problematic because of its adverse effect on chlorate elimination. Chlorates also act locally as a GI irritant and cause mild CNS depression after absorption (Chap. 124).62
Clinical signs and symptoms of chlorate poisoning usually begin 1 to 4 hours after ingestion.102 The earliest manifestations are nausea, vomiting, diarrhea, and crampy abdominal pain. Subsequently, the patient exhibits cyanosis from the methemoglobinemia and black-brown urine from the hemoglobinuria. Obtundation and anuria ensue. Laboratory studies demonstrate methemoglobinemia, anemia, Heinz bodies, ghost cells, fragmented spherocytes, metabolic acidosis, thrombocytopenia, and abnormal coagulation.53 Hyperkalemia is particularly problematic if the patient ingests potassium chlorate preparations.140 In a case of chlorate poisoning from the ingestion of 120 potassium chlorate–containing matchsticks, an MRI revealed symmetric abnormal signal intensity within the deep gray matter and medial temporal lobes.140 This finding can be explained by the increased vulnerability to oxygen deprivation of the basal ganglia. Follow-up MRI 2 months later was normal.
In symptomatic patients with chlorate ingestions, it is reasonable to pursue GI decontamination.73 The utility of methylene blue in the treatment of symptomatic chlorate-induced methemoglobinemia has been questioned as a consequence of the inactivation by chlorates of glucose-6-phosphate dehydrogenase, an enzyme that is required for methylene blue to effectively reduce methemoglobin.191,200 Nevertheless, more recent experience suggests that early use of methylene blue prior to the onset of hemolysis is beneficial due to the necessity of the intact erythrocyte for methylene blue to be efficacious and thus a reasonable treatment.19,111 Exchange transfusion and hemodialysis are reasonable in the treatment of patients with severe chlorate poisoning.144,200 Because the chlorate ion is easily dialyzable, hemodialysis will be effective in removal of chlorate as well as in treating concomitant AKI.92,102,110
Many of the more toxic xenobiotics, such as iodine, phenol, and chlorates, are no longer commonly used as cleansers but are still available in some health care and occupational settings.
Formaldehyde exposures, though also uncommon, cause significant respiratory toxicity and is potentially carcinogenic.
Frequently employed antiseptics, are chlorhexidine, octylphenoxyethoxyethyl ether sulfonate, and many of the currently used quaternary ammonium compounds. Iodine, phenol, and quaternary ammonium compounds are caustic when ingested.
Ingestions of the iodophors do not usually cause significant toxicity, but absorption through other routes produces significant adverse effects.
Ingestion of concentrated hydrogen peroxide results in life-threatening injuries. Boric acid causes a dermatitis.
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