This cationic biguanide has been in use as an antiseptic since the early 1950s. It is found in a variety of skin cleansers, usually as a 4% emulsion (Hibiclens), and may also be found in mouthwash. Chlorhexidine is reported to have low toxicity.
Few cases of deliberate ingestion of chlorhexidine are reported. Symptoms are usually mild, and gastrointestinal irritation is the most likely effect after ingestion.26 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.123 In the same case, liver enzymes concentrations rose to30 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.50 An 80 year-old woman with dementia ingested 200 mL of a 5% chlorhexidine solution and subsequently aspirated.78 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),87 and hemolysis, although the latter may be caused by the hypotonicity of the injected solution.27 Inhalation of vaporized chlorhexidine causes methemoglobinemia, likely as a consequence of the conversion of chlorhexidine to p-chloraniline.199 In one patient, the rectal administration of 4% chlorhexidine resulted in acute colitis with ulcerations.67
Topical absorption of chlorhexidine is negligible. Contact dermatitis is reported in up to 8% of patients who received repetitive topical applications of chlorhexidine.68 More ominously, anaphylactic reactions, including shock, are associated with dermal application.7,141 Some of these cases of chlorhexidine-related anaphylaxis occurred during surgery, appearing 15 to 45 minutes after application of the antiseptic.13 Eye exposure may result in corneal damage.193
Treatment guidelines for chlorhexidine exposure are similar to those for other potential caustics (Chap. 106). Patients with significant symptoms may require endoscopy, but the need for such extensive evaluation is quite uncommon.
Hydrogen peroxide, an oxidizer with weak antiseptic properties, has been used for many years as an antiseptic and a disinfectant.202 This oxidizer is generally available in two 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 sometimes 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 a health food additive to aerate health food drinks.84 This potentially dangerous therapy is touted as a treatment for a variety of conditions, including AIDS and cancer.
Toxicity from hydrogen peroxide may occur after ingestion, inhalation, injection, wound irrigation, rectal administration, dermal exposure and ocular exposure.202 Hydrogen peroxide has two 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 can result in life-threatening embolization. The ingestion of two sips of 33% hydrogen peroxide resulted in cerebral gas embolization and hemiplegia.164 Gas embolization may be 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 may occur.43 The combination of local tissue injury and gas formation from the ingestion of concentrated hydrogen peroxide may cause abdominal bloating, abdominal pain, vomiting, and hematemesis.53,116 Endoscopy may show esophageal edema and erythema and significant gastric mucosal erosions.154,171
Symptoms consistent with sudden oxygen embolization include rapid deterioration in mental status, cyanosis, respiratory failure, seizures, ischemic ECG changes, and acute paraplegia.55,112 A 2 year-old boy died after ingesting 120 to 180 mL of 35% hydrogen peroxide.29 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.53,84,147 Arterialization of oxygen gas embolization may result in cerebral infarction.177 Encephalopathy with cortical visual impairment23 and bilateral hemispheric infarctions detected by MRI imaging may occur after ingestion of concentrated hydrogen peroxide.86 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.112
Death from intravenous injection of 35% hydrogen peroxide is also reported.105 The use of a concentrated hydrogen peroxide solution as part of a hair highlighting procedure resulted in a severe scalp injury including necrosis of the galea aponeurotica.172
Clinical sequelae from the ingestion of dilute hydrogen peroxide are usually much more benign.43,75 Nausea and vomiting are the most common symptoms.43 A whitish discoloration may be 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.75,129 Portal venous gas embolization may occur as a result of the ingestion of 3% hydrogen peroxide.30,129,158
The use of 3% hydrogen peroxide for wound irrigation may result 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.162 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.175 Multiple cases of acute colitis are reported as a complication of administering 3% hydrogen peroxide enemas.125 The use of 3% hydrogen peroxide as a mouth rinse is associated with the development of oral ulcerations.161 Ophthalmic exposures may result in conjunctival injection, burning pain, and blurry vision.43,124 Optic neuropathy including transient blindness (ability to visualize shadows only) and subsequent optic atrophy from possible inhalational of hydrogen peroxide is described.44 Cough, wheezing, and shortness of breath is associated with occupational exposure to peracetic acid-hydrogen peroxide mixtures used to clean endoscopic equipment.35
A careful examination should be performed to detect any evidence of gas formation. A chest radiograph might reveal gas in the cardiac chambers, mediastinum, or pleural space. An abdominal radiograph might show gas in the GI tract or portal system and define the extent of bowel distension. MRI and CT scan might be useful for detecting brain and spinal cord lesions secondary to gas embolism.6,86,112 Endoscopic evaluation can help determine the extent of mucosal injury.154
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. Dilution with milk or water, although unstudied, is unlikely to be helpful. Nasogastric aspiration of hydrogen peroxide might be helpful if the patient presents immediately after ingestion. Induced emesis is contraindicated and activated charcoal offers no antidotal benefit. Patients with abdominal distension from gas formation should be treated with nasogastric suctioning. Those with clinical or radiographic evidence of gas in the heart should be placed in the Trendelenburg position to prevent gas from blocking the right ventricular outflow tract. Careful aspiration of intracardiac air through a central venous line may be attempted in patients in extremis.29 Case reports suggest that hyperbaric therapy may be useful in cases of life-threatening gas embolization after hydrogen peroxide ingestion.53,84,112,131,147,199 Asymptomatic patients who unintentionally ingest small amounts of 3% hydrogen peroxide can be safely observed at home.
Iodine is one of the oldest topical antiseptics.173 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 tincture of iodine, allows substantially more concentrated forms of I2 to be available. 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.45
Iodophors have molecular iodine compounded to a high-molecular-weight carrier or to a solubilizing agent. Povidone-iodine (Betadine), 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).18,68
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.36 Iodine is cytotoxic and 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.68
There may be significant systemic absorption of iodine from topical iodine or iodophor preparations.149 Markedly elevated iodine concentrations occur in patients who receive topical iodophor treatments to areas of dermal breakdown, such as burn injuries.102 Significant absorption occurs when iodophors are applied to the vagina, perianal fistulas, umbilical cords, and the skin of low-birth-weight neonates.184 The mucosal application of povidone-iodine during a hysteroscopy procedure resulted in acute kidney injury (AKI) that transiently required hemodialysis.17 A fatality following intraoperative irrigation of a hip wound with povidone-iodine is also reported.37 In this latter case, the postmortem serum iodine concentration was 7000 μg/dL (normal: 5–8 μg/dL).
Problems associated with the use of iodine include unpleasant odor, skin irritation, allergic reactions, and clothes staining. Ingestion of iodine may cause abdominal pain, vomiting, diarrhea, GI bleeding, delirium, hypovolemia, anuria, and circulatory collapse. Severe caustic injury of the GI tract may occur. The ingestion of approximately45 mL of a 10% iodine solution resulted in death from multisystem failure 67 hours after ingestion.46 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.119
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.100 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 μg/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.102,150 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.150 Metabolic acidosis associated with a high lactate concentration after iodine ingestion likely reflects tissue destruction.36
Electrolyte abnormalities also may 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 iodine’s interference 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.36 Spurious hyperchloremia from iodine (or iodide) may result in the calculation of a low or negative anion gap (Chap. 19).24,52
Other problems associated with topical absorption of iodine-containing preparations are hypothyroidism (particularly in neonates),24,180 hyperthyroidism,160,165 elevated liver enzyme concentrations, neutropenia anaphylaxis,1 and hypoxemia.36 Because of the lack of consistency between iodine concentrations and symptomatology, and because many of these patients had significant secondary medical problems that may have accounted for 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 was the chlorhexidine group.109
Contact dermatitis can result from repetitive applications of iodophors.120 A dermal burn may result from the trapping of an iodophor solution under the body of a patient in a pooled dependent position or under a tourniquet.111,135
The patient who ingests iodine (I2) requires expeditious evaluation, stabilization, and decontamination. Careful nasogastric aspiration and lavage may be performed to limit the caustic effect of the iodine if signs of perforation are absent. Irrigation with a starch solution will convert iodine to the much less toxic iodide and, in the process, turn the gastric effluent dark blue-purple. This change in color may serve as a useful guide in determining when lavage can be terminated. If starch is not available, milk may be a useful alternative. Instillation of 100 mL of a solution of 1% to 3% sodium thiosulfate can also be used to convert any remaining iodine to iodide. Early endoscopy may help assess the extent of the gastrointestinal injury.
Most patients with iodophor ingestion require only supportive management. The use of starch or sodium thiosulfate may be considered in symptomatic patients. Hemodialysis and continuous venovenous hemodiafiltration were used successfully to enhance elimination of iodine in a patient with CKD who had become iodine toxic and developed renal deterioration after undergoing continuous mediastinal irrigation with povidone-iodine.95 The benefit of hemodialysis or continuous venovenous hemodiafiltration is unknown in patients with normal renal function and therefore not recommended.
Potassium permanganate (KMnO4) is a violet water-soluble xenobiotic that is usually sold as crystals or tablets or as a 0.01% dilute solution.92 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 may result in local and systemic toxicity.182 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 may occur from free radicals generated by absorbed permanganate ions.208
Following ingestion, initial symptoms include nausea and vomiting. Laryngeal edema and ulceration of the mouth, esophagus, and, to a lesser extent, the stomach, may result from the caustic effects. Airway obstruction and fatal gastrointestinal perforation and hemorrhage may occur.42,126,143 Esophageal strictures and pyloric stenosis are potential late complications.98
Although potassium permanganate is not well absorbed from theGI tract, systemic absorption may occur, resulting in life-threatening toxicity. Systemic effects include hepatotoxicity, AKI, methemoglobinemia, hemolysis, hemorrhagic pancreatitis, airway obstruction, ARDS, disseminated intravascular coagulation, and cardiovascular collapse.107,118,126,143 Elevation in blood or serum manganese concentration may also occur, confirming systemic absorption (normal concentrations blood manganese 3.9–15.0 μg/L; serum manganese 0.9–2.9 μg/L).
Chronic ingestion of potassium permanganate may result in classic manganese poisoning (manganism) characterized by behavioral changes, hallucinations, and delayed onset of parkinsonianlike symptoms. A 66 year-old man who mistakenly 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’s neurologic examination displayed extrapyramidal signs consistent with parkinsonism (Chap. 97).82
Because the consequential effects of potassium permanganate ingestion are a result of its liberation of strong alkalis, the initial treatment of such a patient should include assessment for evidence of airway compromise. Dilution with milk or water may be useful. Patients with symptoms consistent with caustic injury should undergo early upper GI endoscopy.92 Corticosteroids along with antibiotics may be warranted if laryngeal edema is present. Analysis of liver enzymes, BUN, creatinine, lipase, serum manganese, and methemoglobin concentrations should be performed when systemic toxicity is suspected. Methemoglobinemia, if clinically significant, should be treated with methylene blue (Antidotes in Depth: A42). Dermal irrigation with dilute oxalic acid may be successful in removing cutaneous staining.182 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, has been suggested, but clinical trials have not been performed.208