POTASSIUM PERMANGANATE

Classification | Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

Specific Substances

1) Potassium permanganate
2) Cairox
3) Chameleon mineral
4) Condy's crystals
5) Kaliumpermanganaat (Dutch)
6) Kaliumpermanganat (German)
7) Permanganate de potassium (French)
8) Permanganate of potash
9) Permanganato potasico (Spanish)
10) Permanganic acid potassium salt
11) Permanganic acid, potassium salt
12) Potassio (permanganato di) (Italian)
13) Potassium (permanganate de) (French)
14) Purple salt
15) KMnO4
16) CAS 7722-64-7

1.2.1) MOLECULAR FORMULA
1) KMnO4
2) H-Mn-O4.K

Available Forms Sources

1) At room temperature, potassium permanganate exists as dark purple or bronze-colored, odorless, sweetish, astringent tasting orthorhombic crystals that are almost opaque by transmitted light and have a blue, metallic sheen by reflected light. It is readily soluble in water; aqueous solutions are pink to violet in color, depending on concentration, and slowly deposit manganese dioxide (HSDB, 2004; Budavari, 2001; Lewis, 2001; Lewis, 2000; Lewis, 1998; Freeman, 1998).
2) Available grades include technical, CP (chemically pure), reagent (99+% pure), and USP(CHRIS, 2004; Lewis, 2001a).
3) Formulations include ready-to-use solutions, pellets, tablets, crystals, and powder (HSDB, 2004).

1) Potassium permanganate is produced from manganese ore by electrolytic oxidation (Budavari, 2001; Lewis, 2001a).
2) It may be prepared by oxidizing manganese dioxide with potassium chlorate in potassium hydroxide solution, then completing the oxidation with chlorine or air and carbon dioxide (HSDB, 2004).
3) It is manufactured by a two-step process of thermal oxidation of manganese oxide (from ore) into potassium manganate, followed by electrolytic oxidation to potassium permanganate (HSDB, 2004).
4) The reaction between manganese ore and potassium hydroxide by thermal oxidation and electrolytic oxidation produces potassium permanganate (Ashford, 2001).
5) Treatment of a hot solution of manganate with carbon dioxide will, on cooling, result in the precipitation of potassium permanganate crystals (Lewis, 2001a).
6) It may be manufactured by roasting processes that use manganese(IV) oxide and potassium hydroxide in a molar ratio of 1:2 to 1:3, then heating to 300-400 degrees C, and exposure to secondary oxidation at 190-210 degrees C (HSDB, 2004).
7) A liquid-phase process can be used to manufacture potassium permanganate where manganese(IV) oxide and potassium hydroxide are in a molar ratio greater than or equal to 1:5. The molten mixture (at 200-350 degrees C) is oxygenated, and then the product may be obtained through separation (HSDB, 2004).

1) Potassium permanganate's industrial uses include bleaching resins, waxes, fats, oils, straw, cotton, silk and other fibers and chamois skins; dyeing wood; printing fabrics; purifying air and water; decontamination of skin; treatment of eczema; etching rubber and plastic; surface treatment of steel (especially in wire manufacture); and tanning leathers. It is also used as a fungicide; insecticide; miticide; algicide; bacteriocide; germicide; antiseptic; oxidizer; disinfectant; deodorant; sanitizer; chemical in photography; and reagent in analytical and synthetic organic chemistry (Goldfrank et al, 2002; HSDB, 2004; Pohanish, 2002; Budavari, 2001; Lewis, 2001; Lewis, 1998).
2) Therapeutically, potassium permanganate is used as a topical anti-infective. In veterinary medicine it is used as a topical antiseptic, astringent, and deodorant (Budavari, 2001).
3) Illicit uses have included the production of drugs of abuse, and induction of abortion by topical application to the vaginal wall (21 CFR 250.108, 2003; Lewis, 2000; Lewis, 2000; Lewis, 1998).
4) Historically, potassium permanganate has been used as a urethral irrigant, lavage fluid for alkaloid poisoning, and remedy for snakebites (Goldfrank et al, 2002).

Overview

Life Support

Clinical Effects

0.2.1)

A) USES: Potassium permanganate is an antiseptic and astringent agent with powerful oxidizing effects. Industrial uses include bleaching resins, waxes, fats, oils, straw, cotton, silk and other fibers and chamois skins. It is also used as a disinfectant, deodorant, sanitizer, chemical in photography, and reagent in analytical and synthetic organic chemistry. Illicit uses have included the production of drugs of abuse and induction of abortion by topical application to the vaginal wall. Historically, potassium permanganate has been used as a urethral irrigant, and lavage fluid for alkaloid poisoning.
B) TOXICOLOGY: Potassium permanganate reacts with water to yield manganese dioxide, potassium hydroxide, and oxygen. Potassium hydroxide is a strong alkaline corrosive. In severe cases, systemic effects including disseminated intravascular coagulation (DIC), methemoglobinemia, hepatitis, pancreatitis, and acute renal failure may occur and are possibly caused by free radical generation. Chronic ingestion may cause neurotoxicity, including paresthesias, tremor, and Parkinsonism due to manganese toxicity. Neurotoxicity from manganese results from dopamine depletion and production of the neurotoxins, dopamine quinone and hydrogen peroxide.
C) EPIDEMIOLOGY: Patients may be exposed to potassium permanganate by occupational contact or illicit uses.
D) WITH POISONING/EXPOSURE

1) MILD TO MODERATE TOXICITY: Skin contact with concentrated solutions may cause severe irritation and burns. Contact with diluted solutions can cause purple brown staining of the skin and hardening of the outer layer of the skin. Potassium permanganate may be irritating to the respiratory tract, causing upper airway edema, chest tightness, and coughing. Caustic injury to the mouth and gastrointestinal tract may also occur after ingestion. Eye exposure can cause conjunctival discoloration and corneal and conjunctival burns.
2) SEVERE TOXICITY: Severe gastrointestinal burns have been reported after ingestion. Patients may also develop adult respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC), methemoglobinemia, tachycardia, hypotension, metabolic acidosis, coagulopathy, hepatic necrosis, pancreatitis, and acute renal failure. Strictures and gastric outlet obstruction may develop as delayed complications following gastrointestinal burns. Chronic ingestion may cause neurotoxicity, paresthesias, tremor, and Parkinsonism due to manganese toxicity. Potassium permanganate use as an abortifacient may result in vaginal or cervical burns and erosions, with extensive bleeding, shock, severe scarring and miscarriage as possible complications.

0.2.21)

A) At the time of this review, no studies were found on the possible carcinogenic activity of potassium permanganate in humans or experimental animals.

Laboratory Monitoring

Treatment Overview

0.4.2)

A) MANAGEMENT OF MILD TO MODERATE TOXICITY

1) Treatment consists primarily of symptomatic and supportive care. Monitor for respiratory distress and systemic toxicity. Early gastrointestinal endoscopy to evaluate for burns. Endoscopy should be performed within the first 24 hours postingestion (preferably within 12 hours), and should be avoided from 2 days to 2 weeks postingestion since wound tensile strength is lowest and the risk of perforation highest during this time. Dilution with milk or water may be cautiously recommended. If a patient can protect their airway, immediately dilute with 4 to 8 ounces (120 to 240 mL) of water or milk (not to exceed 4 ounces/120 mL in a child). However, some clinicians have had experience with precipitation of vomiting from dilution. For a large recent ingestion, consider inserting a small flexible nasogastric tube and aspirate stomach contents. Manage mild hypotension with IV fluids.

B) MANAGEMENT OF SEVERE TOXICITY

1) Treatment consists primarily of symptomatic and supportive care. Treat severe hypotension with IV 0.9% NaCl at 10 to 20 mL/kg. Add dopamine or norepinephrine if unresponsive to fluids. In patients with respiratory distress or dyspnea, administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists if bronchospasm develops. Obtain a methemoglobin level in cyanotic patients. Treat symptomatic methemoglobinemia (usually at methemoglobin levels above 20% to 30%) with methylene blue and oxygen therapy. N-acetylcysteine has been used in the treatment of potassium permanganate induced hepatotoxicity, but efficacy has not been established. Monitor blood manganese level in patients with chronic potassium permanganate ingestion who have abnormal neurologic symptoms. Chelation with EDTA and sodium para-aminosalicylic acid has been used in patients with manganese intoxication. However, there is no experience with potassium permanganate exposure and the effectiveness of chelation treatment in improving existing neurological findings or preventing neurologic deterioration has not been clearly demonstrated.

C) DECONTAMINATION

1) ORAL EXPOSURE: The role of gastric decontamination is unclear. Due to the irritant nature of this substance, do not induce vomiting. Neutralization, gastric lavage, and activated charcoal are all contraindicated. In patients without vomiting or respiratory distress who are able to swallow, dilute with milk/water shortly after ingestion; then NPO until after endoscopy. EYE EXPOSURE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water until pH is neutral. If irritation, pain, swelling, lacrimation, or photophobia persists after 15 minutes of irrigation, an ophthalmologic examination should be performed. DERMAL EXPOSURE: Remove contaminated clothes, brush off particulate corrosives, follow with copious irrigation. A physician may need to examine the area if irritation or pain persists. INHALATIONAL EXPOSURE: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer 100% humidified supplemental oxygen. Administer inhaled beta adrenergic agonists if bronchospasm develops.

D) ENDOSCOPIC PROCEDURE

1) Endoscopy should be performed within the first 24 hours postingestion (preferably within 12 hours), and should be avoided from 2 days to 2 weeks postingestion since wound tensile strength is lowest and the risk of perforation highest during this time. Endoscopy should be performed in any patient with deliberate ingestion, adults with any signs or symptoms attributable to inadvertent ingestion, and in children with stridor, vomiting, or drooling after inadvertent ingestion. Endoscopy should also be considered in children with dysphagia or refusal to swallow, significant oral burns, or abdominal pain after unintentional ingestion. Children and adults who are asymptomatic after inadvertent ingestion do not require endoscopy. The grade of mucosal injury at endoscopy is the strongest predictive factor for the occurrence of systemic and GI complications and mortality. The absence of visible oral burns does NOT reliably exclude the presence of esophageal burns. If second or third degree burns are found, follow 10 to 20 days later with barium swallow or esophagram.

E) AIRWAY MANAGEMENT

1) Ensure adequate ventilation and perform endotracheal intubation early in patients with upper airway injury.

F) ANTIDOTE

1) Treat symptomatic methemoglobinemia (usually at methemoglobin levels above 20% to 30%) with methylene blue. N-acetylcysteine has been used in the treatment of potassium permanganate induced hepatotoxicity, but efficacy has not been established.

G) METHEMOGLOBINEMIA

1) Initiate oxygen therapy. Treat with methylene blue if patient is symptomatic (usually at methemoglobin concentrations greater than 20% to 30% or at lower concentrations in patients with anemia, underlying pulmonary or cardiovascular disease). METHYLENE BLUE: INITIAL DOSE/ADULT OR CHILD: 1 mg/kg IV over 5 to 30 minutes; a repeat dose of up to 1 mg/kg may be given 1 hour after the first dose if methemoglobin levels remain greater than 30% or if signs and symptoms persist. NOTE: Methylene blue is available as follows: 50 mg/10 mL (5 mg/mL or 0.5% solution) single-dose ampules and 10 mg/1 mL (1% solution) vials. Additional doses may sometimes be required. Improvement is usually noted shortly after administration if diagnosis is correct. Consider other diagnoses or treatment options if no improvement has been observed after several doses. If intravenous access cannot be established, methylene blue may also be given by intraosseous infusion. Methylene blue should not be given by subcutaneous or intrathecal injection. NEONATES: DOSE: 0.3 to 1 mg/kg.

H) ENHANCED ELIMINATION

1) It is unknown if hemodialysis would remove potassium permanganate. Dialysis should not be routinely recommended.

I) PATIENT DISPOSITION

1) HOME CRITERIA: Patients who are asymptomatic after inadvertent exposure to small amounts and are otherwise improving may be managed at home.
2) OBSERVATION CRITERIA: Patients with a deliberate ingestions, and those who are symptomatic need to be monitored until they are clearly improving and clinically stable.
3) ADMISSION CRITERIA: Patients with severe symptoms should be admitted for treatment and monitoring. Patients with respiratory failure, GI burns, hemodynamic instability, gastrointestinal bleeding, or large ingestions should be admitted to an intensive care setting.
4) CONSULT CRITERIA: Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear. Patients with severe eye irritation/burns should be evaluated by an ophthalmologist. Consult a gastroenterologist to perform endoscopy to evaluate for any GI injury and determine prognosis for guiding further management. Patients with severe or extensive dermal burns should be evaluated by a burn specialist.

J) PITFALLS

1) Failure to detect airway compromise and properly manage airways. Failure to detect/recognize methemoglobinemia, hemolysis, ARDS, pancreatitis, hepatitis, and acute renal injury.

K) DIFFERENTIAL DIAGNOSIS

1) Nitrogen dioxide toxicity, methemoglobin-inducing agent toxicity, salicylate toxicity, naphthalene toxicity, caustic ingestion, and acute pancreatitis.

0.4.4)

A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
B) CAUSTIC EYE DECONTAMINATION: Immediately irrigate each affected eye with copious amounts of water or sterile 0.9% saline for about 30 minutes. Irrigating volumes up to 20 L or more have been used to neutralize the pH. After this initial period of irrigation, the corneal pH may be checked with litmus paper and a brief external eye exam performed. Continue direct copious irrigation with sterile 0.9% saline until the conjunctival fornices are free of particulate matter and returned to pH neutrality (pH 7.4). Once irrigation is complete, a full eye exam should be performed with careful attention to the possibility of perforation.
C) EYE ASSESSMENT: The extent of eye injury (degree of corneal opacification and perilimbal whitening) may not be apparent for 48 to 72 hours after the burn.

0.4.5)

A) OVERVIEW

1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

Clinical Effects

Summary Of Exposure

Vital Signs

3.3.4)

A) WITH POISONING/EXPOSURE

1) HYPERTENSION: Transient hypertension has been reported after ingestion and injection (Lustig et al, 1982; Middleton et al, 1990).
2) HYPOTENSION: Profound hypotension and circulatory collapse may develop in severe cases (Ong et al, 1997; Young et al, 1996; Middleton et al, 1990).

3.3.5)

A) WITH POISONING/EXPOSURE

1) TACHYCARDIA: Tachycardia may develop in patients with serious exposure (Mahomedy et al, 1975; Middleton et al, 1990; Lustig et al, 1982).

Heent

3.4.3)

A) WITH POISONING/EXPOSURE

1) BURNS

a) A 22-year-old man sustained potassium permanganate burns to both eyes. Initial exam revealed extensive brownish discoloration of the conjunctiva, decreased visual acuity (20/200 both eyes), corneal clouding and fluorescein uptake, subconjunctival hemorrhages and small areas of conjunctival necrosis. The eyes were irrigated until pH was 8 and the patient treated with systemic and topical steroids. Recovery was complete in one month (Michaels & Zugsmith, 1973).
b) A 45-year-old man was splashed in both eyes with a concentrated solution of potassium permanganate. Following ocular irrigation, a slit lamp examination revealed the presence of foreign-body type irritation and the presence of several hard eroded lesions that appeared as granular deposits on the conjunctival tissue. The deposits were removed manually and a 5% ascorbic acid solution was used to irrigate the eyes and to dissolve the remaining granulated deposits. There was no residual damage from the treatment and the patient was released. No additional follow-up was presented (Sigg et al, 1998).

2) DIPLOPIA: A 66-year-old man was mistakenly administered approximately 10 grams of potassium permanganate over 4 weeks. He developed occasional diplopia when looking upward and to the right (Holzgraefe et al, 1986).

3.4.6)

A) WITH POISONING/EXPOSURE

1) DISCOLORATION: Purple-brown staining of the mouth and tongue is common after ingestion (Southwood et al, 1987; Middleton et al, 1990; Lifshitz et al, 1999).
2) BURNS: Burns and edema of the oral mucosa and tongue may develop after ingestion (Southwood et al, 1987; Young et al, 1996; Ong et al, 1997; Lifshitz et al, 1999).

Cardiovascular

3.5.2)

A) HYPERTENSIVE EPISODE

1) WITH POISONING/EXPOSURE

a) Transient hypertension has been reported after ingestion and injection (Lustig et al, 1982; Middleton et al, 1990).

B) HYPOTENSIVE EPISODE

1) WITH POISONING/EXPOSURE

a) Profound hypotension and circulatory collapse may develop in severe cases (Gawarammana et al, 2009; Lifshitz et al, 1999; Ong et al, 1997; Young et al, 1996; Middleton et al, 1990).
b) Bradycardia and profound hypotension occurred in an infant who ingested an unknown amount of a 0.01% solution (Lifshitz et al, 1999).

C) TACHYCARDIA

1) WITH POISONING/EXPOSURE

a) Tachycardia may develop in patients with serious exposure (Mahomedy et al, 1975; Middleton et al, 1990; Lustig et al, 1982).

D) PERICARDIAL EFFUSION

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 68-year-old man developed radiological evidence of a pericardial effusion two days after injecting 7 grams of potassium permanganate dissolved in tap water into his fifth left intercostal space in the midclavicular line (Lustig et al, 1982).

Respiratory

3.6.2)

A) INJURY OF UPPER RESPIRATORY TRACT

1) WITH POISONING/EXPOSURE

a) Stridor and upper airway burns and edema may develop after ingestion (Justus & Gastmeier, 1967; Young et al, 1996; Ong et al, 1997; Southwood et al, 1987).

B) ACUTE LUNG INJURY

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 75-year-old man developed adult respiratory distress syndrome (ARDS) after ingesting approximately 20 grams of potassium permanganate (Middleton et al, 1990).
b) CASE REPORT: An 8-week-old infant developed acute respiratory distress syndrome, seen on chest x-ray, following the ingestion of an unknown amount of a 0.01% solution of potassium permanganate. The infant died 28 hours after admission (Lifshitz et al, 1999).

C) PLEURAL EFFUSION

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 68-year-old man developed radiological evidence of a pleural effusion one day after injecting 7 grams of potassium permanganate dissolved in tap water into his fifth left intercostal space in the midclavicular line (Lustig et al, 1982). Multiple encapsulated pneumothoraces developed after several days.

D) EDEMA OF LARYNX

1) WITH POISONING/EXPOSURE

a) Laryngeal strictures have been reported as delayed (by weeks or more) complications after ingestion of potassium permanganate (Wang, 1994).

Neurologic

3.7.2)

A) PARESTHESIA

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 66-year-old man was mistakenly administered approximately 10 grams of potassium permanganate over 4 weeks. He developed paresthesias and hypesthesias of the right side of his body, with reduced proprioception and vibratory sensation in the right hand and foot (Holzgraefe et al, 1986).

B) TREMOR

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 66-year-old man was mistakenly administered approximately 10 grams of potassium permanganate over 4 weeks. He developed a resting tremor of his left hand and widespread muscle fasciculations (Holzgraefe et al, 1986).

C) COMA

1) WITH POISONING/EXPOSURE

a) Coma and decreased level of consciousness have been described as a late finding in patients with severe methemoglobinemia secondary to potassium permanganate ingestion (Mahomedy et al, 1975).

D) EXTRAPYRAMIDAL DISEASE

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 66-year-old man was mistakenly administered approximately 10 grams of potassium permanganate over 4 weeks. Nine months later he had developed evidence of a Parkinson syndrome including resting tremor, slow grade rigor of the extremities and gait shortening (Holzgraefe et al, 1986).

Gastrointestinal

3.8.2)

A) CHEMICAL BURN

1) WITH POISONING/EXPOSURE

a) Severe burns of the esophagus, stomach, and in severe cases small intestines may develop after ingestion (Lifshitz et al, 1999; Young et al, 1996; Holzgraefe et al, 1986; Middleton et al, 1990; Desmul et al, 1968; Mayer et al, 1972).
b) Burns may be difficult to distinguish from potassium permanganate staining of tissues (Southwood et al, 1987).
c) In severe cases perforation may develop (Guichardiere, 1965).

B) STRICTURE OF ESOPHAGUS

1) WITH POISONING/EXPOSURE

a) Esophageal strictures and gastric outlet obstruction have been reported as delayed (by weeks) complications of potassium permanganate ingestion (Dagli et al, 1973; Kochhar et al, 1986; Wang, 1994).

C) PANCREATITIS

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 75-year-old man developed severe abdominal pain, hyperglycemia and elevated serum amylase levels (3752 U/liter) after ingesting approximately 20 grams of potassium permanganate. Severe hemorrhagic pancreatitis was confirmed on autopsy (Middleton et al, 1990).

D) INJURY OF STOMACH

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 42-year-old man presented with severe epigastric pain and multiple episodes of coffee ground vomiting about 12 hours after ingesting 20 g of a household antiseptic, containing potassium permanganate dissolved in 300 mL of water. He had purple discoloration of the tongue with significant uvular swelling. Laboratory results showed an elevated white cell count of 15,000 cells/mm(3) and CT scan of the chest, abdomen, and pelvis showed significant gastric wall thickening and perigastric fat streaking extending to the duodenal loop, and peripancreatic and perihepatic free fluid. About 17 hours postingestion, esophagogastroduodenoscopy showed a normal esophagus, patchy black necrosis of the gastric fundus and body with antral ulcerations. Following supportive care, including IV fluids, a proton pump inhibitor, and antibiotics, his condition gradually improved and he was discharged 4 days later (Younan et al, 2013).

E) ABDOMINAL PAIN

1) WITH POISONING/EXPOSURE

a) Abdominal pain may persist for weeks after ingestion (Guichardiere, 1965).
b) CASE REPORT: A 42-year-old man presented with severe epigastric pain and multiple episodes of coffee ground vomiting about 12 hours after ingesting 20 g of a household antiseptic, containing potassium permanganate dissolved in 300 mL of water. He had purple discoloration of the tongue with significant uvular swelling. Laboratory results showed an elevated white cell count of 15,000 cells/mm(3) and CT scan of the chest, abdomen, and pelvis showed significant gastric wall thickening and perigastric fat streaking extending to the duodenal loop, and peripancreatic and perihepatic free fluid. About 17 hours postingestion, esophagogastroduodenoscopy showed a normal esophagus, patchy black necrosis of the gastric fundus and body with antral ulcerations. Following supportive care, including IV fluids, a proton pump inhibitor, and antibiotics, his condition gradually improved and he was discharged 4 days later (Younan et al, 2013).

F) GASTRIC HEMORRHAGE

1) WITH POISONING/EXPOSURE

a) CASE SERIES: In Sri Lanka, intentional ingestion of a laundry detergent containing a sachet each of 12.5 g oxalic acid and 1.2 g potassium permanganate resulted in 115 cases of toxicity with 18 fatalities. Gastrointestinal symptoms developed within 24 hours of ingestion. Of the individuals that ingested oxalic acid only, a case fatality ratio of 25.4% was observed, while a case fatality ratio of 9.8% occurred in patients ingesting both oxalic acid and potassium permanganate. No deaths occurred in the potassium permanganate only group. Most deaths occurred within one hour of ingestion. Postmortem exam revealed macroscopic evidence of superficial erosions of the esophagus, oropharynx and larynx in each case (Gawarammana et al, 2009).

G) ESOPHAGEAL INJURY

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 5-year-old boy presented to the ED after ingesting a "small amount" of potassium permanganate. He had purple/brown staining of his lips, teeth, tongue, and hands and was drooling. His posterior oropharynx was clear and phonation was normal. His airway was intact but his lips were markedly swollen. All laboratory tests, chest radiograph and abdominal series were normal. The patient was started on ampicillin and ranitidine 25 mg IV every 8 hours and solumedrol and was kept NPO. Endoscopy was performed the next morning and revealed diffuse black staining of the esophagus and stomach and evidence of gastritis. Endoscopy repeated the following day revealed clear-cut ulcerations of the middle and distal esophagus and gastritis without erosions. Blood work remained normal and the patient was discharged 48 hours after ingestion on ranitidine 50 mg every 8 hours and a regular diet. No long-term adverse sequelae were observed at follow-up 1 year later (Johnson & Cassidy, 2004).

Hepatic

3.9.2)

A) HEPATIC FAILURE

1) WITH POISONING/EXPOSURE

a) Hepatic injury has been described after ingestion and injection (Lustig et al, 1982; Middleton et al, 1990; Lifshitz et al, 1999). In severe cases fulminant hepatic failure and necrosis may develop (Ong et al, 1997; Young et al, 1996).
b) CASE REPORT: A 24-year-old woman ingested an unknown quantity of potassium permanganate. She developed upper airway edema and upper esophageal staining and possibly burns shortly after ingestion. Thirty six hours after admission she developed hypotension requiring fluid loading and epinephrine infusion, disseminated intravascular coagulation, and deteriorating liver function tests. By 48 hours after admission she had fulminant hepatic failure and over the next day progressed to oliguric renal failure and ARDS. She died on the sixth day of hospitalization. Autopsy showed severe fatty change and necrosis of the liver, esophagitis, gastritis, and acute renal tubular necrosis (Young et al, 1996; Ong et al, 1997).

Genitourinary

3.10.2)

A) RENAL FAILURE SYNDROME

1) WITH THERAPEUTIC USE

a) Acute renal failure may develop several days after severe poisoning.
b) CASE REPORT: A 24-year-old woman ingested an unknown quantity of potassium permanganate. Thirty-six hours after admission she developed hypotension requiring fluid loading and epinephrine infusion, disseminated intravascular coagulation, and deteriorating liver function tests. By 48 hours after admission she had fulminant hepatic failure and over the next day progressed to oliguric renal failure and ARDS. She died on the sixth day of hospitalization. Autopsy showed acute renal tubular necrosis (Young et al, 1996; Ong et al, 1997).
c) CASE SERIES: In Sri Lanka, intentional ingestion of a laundry detergent containing a sachet each of 12.5 g oxalic acid and 1.2 g potassium permanganate resulted in 115 cases of toxicity with 18 fatalities. Of the individuals that ingested a sublethal dose of oxalic acid and potassium permanganate (n=51), acute renal failure was observed 2 to 3 days after exposure. Median serum creatinine was 1.7 (Interquartile range: 0.91-4.4). Most recovered with supportive care (Gawarammana et al, 2009).

B) ALBUMINURIA

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 68-year-old man developed proteinuria after injecting approximately 7 grams of potassium permanganate in tap water into his fifth intercostal space at the mid clavicular line (Lustig et al, 1982).

C) CHEMICAL BURN

1) WITH POISONING/EXPOSURE

a) BLADDER

1) CASE REPORT: A 23-year-old man performed urethral irrigation with a solution of 25 grams of potassium permanganate dissolved in a teacupful of water over two days. He developed severe urethral and bladder pain, and was unable to void. Urinalysis revealed gross hematuria and proteinuria. On the third day he developed clinical evidence of peritonitis and on the fourth day he died. Autopsy revealed a distended inflamed bladder, adhesive peritonitis from the bladder to the umbilicus, and severe burns of the bladder and urethra (Willimott, 1936).

b) CERVIX

1) Insertion of potassium permanganate tablets into the vagina to induce abortion may result in cervical and/or vaginal burns which may be associated with profuse bleeding. Severe cervical scarring may develop as a delayed complication.
2) CASE SERIES: In a series of 65 cases of suspected use of vaginal potassium permanganate, 34 patients required vaginal packing to control bleeding, 10 required suturing, 12 developed shock secondary to severe bleeding, and 6 were successful in producing abortion (McDonough, 1945).
3) CASE REPORT: A 34-year-old woman who was 4 months pregnant presented in shock (blood pressure 70/30 mm Hg, pulse 140 beats/minute) with severe vaginal bleeding after suspected use of potassium permanganate to induce abortion. Examination revealed bright red blood coming from a crater on the posterior lip of the cervix extending to the posterior fornix. Bleeding was controlled with sutures. Severe cervical scarring necessitated cesarean section at term (McDonough, 1945).

a) COMMENTARY: Potassium permanganate crystals were poured deep into the vagina, using a tampon cardboard tube, for the purpose of inducing an abortion. Vaginal perforation occurred, but the patient survived and subsequently had children (Tipton, 2000).

Acid-Base

3.11.2)

A) ACIDOSIS

1) WITH POISONING/EXPOSURE

a) Profound metabolic acidosis may be observed in severe cases following ingestions (Lifshitz et al, 1999).

Hematologic

3.13.2)

A) DISSEMINATED INTRAVASCULAR COAGULATION

1) WITH POISONING/EXPOSURE

a) Disseminated intravascular coagulation (DIC) may develop after large ingestions.
b) CASE REPORT: A 24-year-old woman ingested an unknown quantity of potassium permanganate. Thirty six hours after admission she developed hypotension requiring fluid loading and epinephrine infusion, disseminated intravascular coagulation (thrombocytopenia, INR 3.7, PTT 75 seconds) and deteriorating liver function tests. By 48 hours after admission she had fulminant hepatic failure and over the next day progressed to oliguric renal failure and ARDS. She died on the sixth day of hospitalization. Autopsy showed petechial hemorrhages in the brain and kidney (Young et al, 1996; Ong et al, 1997).

B) METHEMOGLOBINEMIA

1) Severe methemoglobinemia may develop after exposure.
2) CASE REPORT: Two women developed mental status depression, hypotension, tachycardia and cyanosis with methemoglobinemia after ingesting mixtures of soot and potassium permanganate. Both recovered rapidly with methylene blue therapy (Mahomedy et al, 1975).

Dermatologic

3.14.2)

A) DISCOLORATION OF SKIN

1) WITH POISONING/EXPOSURE

a) Purple brown staining of the skin may develop after contact (Southwood et al, 1987).

B) BURN

1) WITH POISONING/EXPOSURE

a) Skin contact with concentrated solutions may cause severe irritation and burns (Cartotto et al, 1996).

Endocrine

3.16.2)

A) HYPERGLYCEMIA

1) WITH POISONING/EXPOSURE

a) Hyperglycemia has been reported in the setting of acute pancreatitis after potassium permanganate ingestion.
b) CASE REPORT: A 75-year-old man developed severe abdominal pain, hyperglycemia and elevated serum amylase levels (3752 U/liter) after ingesting approximately 20 grams of potassium permanganate. Severe hemorrhagic pancreatitis was confirmed on autopsy (Middleton et al, 1990).

Reproductive

3.20.3)

A) ABORTION

1) The only reports of effects on human reproduction stem from the use of potassium permanganate as an abortifacient by direct application to the vagina, either as tablets or as a douche (Aguilar Guerrero et al, 1971; (Verelli, 1965). Potassium permanganate vaginal application usually does NOT induce abortion, but perforation of the vagina and vaginal bleeding often occur (Aguilar Guerrero et al, 1971; (Verelli, 1965).

B) METHEMOGLOBINEMIA

1) Potassium permanganate is known to rarely induce methemoglobinemia. Methemoglobinemia is particularly dangerous to the fetus because of its increased demand for oxygen, and also because fetal hemoglobin is more easily oxidized to methemoglobin than the adult form and infants can reduce methemoglobin to normal hemoglobin less readily than adults. There is evidence that infants (and presumably the fetus) can be harmed at levels of methemoglobinemia which do not affect adults.

3.20.5)

A) ANIMAL STUDIES

1) Potassium permanganate given for six months at subthreshold doses inhibited spermatogenesis and disturbed oogenesis in rats (Manzhgaladze & Vasakidze, 1972). Developmental defects (increased postnatal mortality, decreased growth, and delayed sexual maturity) were also found. When injected directly into the vas deferens, potassium permanganate caused sterility in male gerbils by occluding the duct (Dixit, 1976). This latter study has no direct relevance to occupational exposure, however.

Carcinogenicity

3.21.1)

A) IARC Carcinogenicity Ratings for CAS7722-64-7 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) Not Listed

3.21.2)

A) At the time of this review, no studies were found on the possible carcinogenic activity of potassium permanganate in humans or experimental animals.

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) Monitor vital signs, liver enzymes, and renal function in patients with significant exposure.
B) Monitor INR or PT, PTT, CBC and platelet counts in patients with severe toxicity.
C) Monitor arterial blood gases, pulse oximetry, and pulmonary function tests, and obtain a chest x-ray in any patient with respiratory symptoms.
D) Monitor methemoglobin levels in symptomatic or cyanotic patients.
E) Potassium permanganate is radiopaque and performing an abdominal radiograph has been proposed as a way to assess the adequacy of gastrointestinal decontamination. However, there is no evidence to support the reliability of this maneuver.

4.1.2)

A) BLOOD/SERUM CHEMISTRY

1) Monitor liver enzymes, and renal function in patients with significant exposure.

B) HEMATOLOGIC

1) Monitor INR or PT, PTT, CBC and platelet counts in patients with severe toxicity.
2) Monitor methemoglobin levels in symptomatic or cyanotic patients.

C) SPECIFIC AGENT

1) Serum manganese levels are often elevated after exposure, but their prognostic value is not clear.

4.1.3)

A) SPECIFIC AGENT

1) Urine manganese levels are often elevated after exposure, but their prognostic value is not clear.

Radiographic Studies

1) Obtain a chest x-ray in patients with severe poisoning or pulmonary effects.

1) Potassium permanganate tablets are radiopaque. Abdominal radiographs may help assess the adequacy of decontamination (Conso et al, 1974; Mayer et al, 1972), however, there is no evidence to support the reliability of this maneuver.

Methods

Treatment

Life Support

Patient Disposition

6.3.1)

6.3.1.1) ADMISSION CRITERIA/ORAL

A) Patients with severe symptoms should be admitted for treatment and monitoring. Patients with respiratory failure, GI burns, hemodynamic instability, gastrointestinal bleeding, or large ingestions should be admitted to an intensive care setting.

6.3.1.2) HOME CRITERIA/ORAL

A) Patients who are asymptomatic after inadvertent exposure to small amounts and are otherwise improving may be managed at home.

6.3.1.3) CONSULT CRITERIA/ORAL

A) Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear. Patients with severe eye irritation/burns should be evaluated by an ophthalmologist. Consult a gastroenterologist to perform endoscopy to evaluate for any GI injury and determine prognosis for guiding further management. Patients with severe or extensive dermal burns should be evaluated by a burn specialist.

6.3.1.5) OBSERVATION CRITERIA/ORAL

A) Patients with a deliberate ingestions, and those who are symptomatic need to be monitored until they are clearly improving and clinically stable.

Monitoring

Oral Exposure

6.5.1)

A) ORAL EXPOSURE

1) The role of gastric decontamination is unclear. Due to the irritant nature of this substance, do not induce vomiting. Neutralization and activated charcoal are all contraindicated.

B) DILUTION

1) If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. The exact ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).
2) USE OF DILUENTS IS CONTROVERSIAL: While experimental models have suggested that immediate dilution may lessen caustic injury (Homan et al, 1993; Homan et al, 1994; Homan et al, 1995), this has not been adequately studied in humans.
3) DILUENT TYPE: Use any readily available nontoxic, cool liquid. Both milk and water have been shown to be effective in experimental studies of caustic ingestion (Maull et al, 1985; Rumack & Burrington, 1977; Homan et al, 1995; Homan et al, 1994; Homan et al, 1993).
4) ADVERSE EFFECTS: Potential adverse effects include vomiting and airway compromise (Caravati, 2004).
5) CONTRAINDICATIONS: Do NOT attempt dilution in patients with respiratory distress, altered mental status, severe abdominal pain, nausea or vomiting, or patients who are unable to swallow or protect their airway. Diluents should not be force fed to any patient who refuses to swallow (Rao & Hoffman, 2002).

C) INHALATION EXPOSURE

1) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
2) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
3) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).

a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)

4) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
5) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
6) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
7) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
8) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).

D) DERMAL EXPOSURE

E) EYE EXPOSURE

1) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.

6.5.2)

A) The role of gastric decontamination is unclear. Due to the irritant nature of this substance, do not induce vomiting. Neutralization, gastric lavage, and activated charcoal are all contraindicated.
B) DILUTION

C) NASOGASTRIC SUCTION

1) For large recent ingestions, consider inserting a small flexible nasogastric tube and aspirating stomach contents.

D) NEUTRALIZATION

1) The use of neutralizing agents after caustic ingestion is NOT recommended. Neutralization has the potential to generate gas and cause exothermic reactions which might worsen injury. Experimental studies suggest that neutralization generates heat, does not limit injury unless performed immediately and that very large volumes of fluid are required to reach neutral pH.

6.5.3)

A) SUPPORT

1) MANAGEMENT OF MILD TO MODERATE TOXICITY

a) Treatment consists primarily of symptomatic and supportive care. Monitor for respiratory distress and systemic toxicity. Early gastrointestinal endoscopy to evaluate for burns. Endoscopy should be performed within the first 24 hours postingestion (preferably within 12 hours), and should be avoided from 2 days to 2 weeks postingestion since wound tensile strength is lowest and the risk of perforation highest during this time. Dilution with milk or water may be cautiously recommended. If a patient can protect their airway, immediately dilute with 4 to 8 ounces (120 to 240 mL) of water or milk (not to exceed 4 ounces/120 mL in a child). However, some clinicians have had experience with precipitation of vomiting from dilution. For a large recent ingestion, consider inserting a small flexible nasogastric tube and aspirate stomach contents. Manage mild hypotension with IV fluids.

2) MANAGEMENT OF SEVERE TOXICITY

a) Treatment consists primarily of symptomatic and supportive care. Treat severe hypotension with IV 0.9% NaCl at 10 to 20 mL/kg. Add dopamine or norepinephrine if unresponsive to fluids. In patients with respiratory distress or dyspnea, administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists if bronchospasm develops. Obtain a methemoglobin level in cyanotic patients. Treat symptomatic methemoglobinemia (usually at methemoglobin levels above 20% to 30%) with methylene blue and oxygen therapy. N-acetylcysteine has been used in the treatment of potassium permanganate induced hepatotoxicity, but efficacy has not been established. Monitor blood manganese level in patients with chronic potassium permanganate ingestion who have abnormal neurologic symptoms. Chelation with EDTA and sodium para-aminosalicylic acid has been used in patients with manganese intoxication. However, there is no experience with potassium permanganate exposure and the effectiveness of chelation treatment in improving existing neurological findings or preventing neurologic deterioration has not been clearly demonstrated.

B) MONITORING OF PATIENT

1) Monitor vital signs, liver enzymes, and renal function in patients with significant exposure.
2) Monitor INR or PT, PTT, CBC and platelet counts in patients with severe toxicity.
3) Monitor arterial blood gases, pulse oximetry, and pulmonary function tests, and obtain a chest x-ray in any patient with respiratory symptoms.
4) Monitor methemoglobin levels in symptomatic or cyanotic patients.
5) Potassium permanganate is radiopaque and performing an abdominal radiograph has been proposed as a way to assess the adequacy of gastrointestinal decontamination. However, there is no evidence to support the reliability of this maneuver.

C) HYPOTENSIVE EPISODE

1) SUMMARY

a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.

2) DOPAMINE

a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).

3) NOREPINEPHRINE

a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
b) DOSE

1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).

D) AIRWAY MANAGEMENT

1) Ensure adequate ventilation and perform endotracheal intubation early in patients with upper airway injury.

E) BURN

1) There is little specific information on the management of burns from potassium permanganate ingestion. The following information is derived from experience with other caustics.
2) SUMMARY: Burns of the oropharynx, esophagus, stomach, and duodenum may occur. Complications such as stricture, perforation, gastrointestinal bleeding and gastric outlet obstruction are related to the depth of burn. Early (within 24 hours) endoscopy should be performed to assess the severity of injury and guide further management.

F) ENDOSCOPIC PROCEDURE

1) SUMMARY: Obtain consultation concerning endoscopy as soon as possible, and perform endoscopy within the first 24 hours when indicated.
2) INDICATIONS: Endoscopy should be performed in adults with a history of deliberate ingestion, adults with any signs or symptoms attributable to inadvertent ingestion, and in children with stridor, vomiting, or drooling after unintentional ingestion (Crain et al, 1984). Endoscopy should also be performed in children with dysphagia or refusal to swallow, significant oral burns, or abdominal pain after unintentional ingestion (Gaudreault et al, 1983; Nuutinen et al, 1994). Children and adults who are asymptomatic after accidental ingestion do not require endoscopy (Gupta et al, 2001; Lamireau et al, 2001; Gorman et al, 1992).
3) RISKS: Numerous large case series attest to the relative safety and utility of early endoscopy in the management of caustic ingestion.

a) REFERENCES: (Dogan et al, 2006; Symbas et al, 1983; Crain et al, 1984a; Gaudreault et al, 1983a; Schild, 1985; Moazam et al, 1987; Sugawa & Lucas, 1989; Previtera et al, 1990; Zargar et al, 1991; Vergauwen et al, 1991; Gorman et al, 1992)

4) The risk of perforation during endoscopy is minimized by (Zargar et al, 1991):

a) Advancing across the cricopharynx under direct vision
b) Gently advancing with minimal air insufflation
c) Never retroverting or retroflexing the endoscope
d) Using a pediatric flexible endoscope
e) Using extreme caution in advancing beyond burn lesion areas
f) Most authors recommend endoscopy within the first 24 hours of injury, not advancing the endoscope beyond areas of severe esophageal burns, and avoiding endoscopy during the subacute phase of healing when tissue slough increases the risk of perforation (5 to 15 days after ingestion) (Zargar et al, 1991).

5) GRADING

a) Several scales for grading caustic injury exist. The likelihood of complications such as strictures, obstruction, bleeding, and perforation is related to the severity of the initial burn (Zargar et al, 1991):
b) Grade 0 - Normal examination
c) Grade 1 - Edema and hyperemia of the mucosa; strictures unlikely.
d) Grade 2A - Friability, hemorrhages, erosions, blisters, whitish membranes, exudates and superficial ulcerations; strictures unlikely.
e) Grade 2B - Grade 2A plus deep discreet or circumferential ulceration; strictures may develop.
f) Grade 3A - Multiple ulcerations and small scattered areas of necrosis; strictures are common, complications such as perforation, fistula formation or gastrointestinal bleeding may occur.
g) Grade 3B - Extensive necrosis through visceral wall; strictures are common, complications such as perforation, fistula formation, or gastrointestinal bleeding are more likely than with 3A.

6) FOLLOW UP - If burns are found, follow 10 to 20 days later with barium swallow or esophagram.
7) SCINTIGRAPHY - Scans utilizing radioisotope labelled sucralfate (technetium 99m) were performed in 22 patients with caustic ingestion and compared with endoscopy for the detection of esophageal burns. Two patients had minimal residual isotope activity on scanning but normal endoscopy and two patients had normal activity on scan but very mild erythema on endoscopy. Overall the radiolabeled sucralfate scan had a sensitivity of 100%, specificity of 81%, positive predictive value of 84% and negative predictive value of 100% for detecting clinically significant burns in this population (Millar et al, 2001). This may represent an alternative to endoscopy, particularly in young children, as no sedation is required for this procedure. Further study is required.
8) MINIPROBE ULTRASONOGRAPHY - was performed in 11 patients with corrosive ingestion . Findings were categorized as grade 0 (distinct muscular layers without thickening, grade I (distinct muscular layers with thickening), grade II (obscured muscular layers with indistinct margins) and grade III (muscular layers that could not be differentiated). Findings were further categorized as to whether the worst appearing image involved part of the circumference (type a) or the whole circumference (type b). Strictures did not develop in patients with grade 0 (5 patients) or grade I (4 patients) lesions. Transient stricture formation developed in the only patient with grade IIa lesions, and stricture requiring repeated dilatation developed in the only patient with grade IIIb lesions (Kamijo et al, 2004).

G) CORTICOSTEROID

1) CORROSIVE INGESTION/SUMMARY: The use of corticosteroids for the treatment of caustic ingestion is controversial. Most animal studies have involved alkali-induced injury (Haller & Bachman, 1964; Saedi et al, 1973). Most human studies have been retrospective and generally involve more alkali than acid-induced injury and small numbers of patients with documented second or third degree mucosal injury.
2) FIRST DEGREE BURNS: These burns generally heal well and rarely result in stricture formation (Zargar et al, 1989; Howell et al, 1992). Corticosteroids are generally not beneficial in these patients (Howell et al, 1992).
3) SECOND DEGREE BURNS: Some authors recommend corticosteroid treatment to prevent stricture formation in patients with a second degree, deep-partial thickness burn (Howell et al, 1992). However, no well controlled human study has documented efficacy. Corticosteroids are generally not beneficial in patients with a second degree, superficial-partial thickness burn (Caravati, 2004; Howell et al, 1992).
4) THIRD DEGREE BURNS: Some authors have recommended steroids in this group as well (Howell et al, 1992). A high percentage of patients with third degree burns go on to develop strictures with or without corticosteroid therapy and the risk of infection and perforation may be increased by corticosteroid use. Most authors feel that the risk outweighs any potential benefit and routine use is not recommended (Boukthir et al, 2004; Oakes et al, 1982; Pelclova & Navratil, 2005).
5) CONTRAINDICATIONS: Include active gastrointestinal bleeding and evidence of gastric or esophageal perforation. Corticosteroids are thought to be ineffective if initiated more than 48 hours after a burn (Howell, 1987).
6) DOSE: Administer daily oral doses of 0.1 milligram/kilogram of dexamethasone or 1 to 2 milligrams/kilogram of prednisone. Continue therapy for a total of 3 weeks and then taper (Haller et al, 1971; Marshall, 1979). An alternative regimen in children is intravenous prednisolone 2 milligrams/kilogram/day followed by 2.5 milligrams/kilogram/day of oral prednisone for a total of 3 weeks then tapered (Anderson et al, 1990).
7) ANTIBIOTICS: Animal studies suggest that the addition of antibiotics can prevent the infectious complications associated with corticosteroid use in the setting of caustic burns. Antibiotics are recommended if corticosteroids are used or if perforation or infection is suspected. Agents that cover anaerobes and oral flora such as penicillin, ampicillin, or clindamycin are appropriate (Rosenberg et al, 1953).
8) STUDIES

a) ANIMAL

1) Some animal studies have suggested that corticosteroid therapy may reduce the incidence of stricture formation after severe alkaline corrosive injury (Haller & Bachman, 1964; Saedi et al, 1973a).
2) Animals treated with steroids and antibiotics appear to do better than animals treated with steroids alone (Haller & Bachman, 1964).
3) Other studies have shown no evidence of reduced stricture formation in steroid treated animals (Reyes et al, 1974). An increased rate of esophageal perforation related to steroid treatment has been found in animal studies (Knox et al, 1967).

b) HUMAN

1) Most human studies have been retrospective and/or uncontrolled and generally involve small numbers of patients with documented second or third degree mucosal injury. No study has proven a reduced incidence of stricture formation from steroid use in human caustic ingestions (Haller et al, 1971; Hawkins et al, 1980; Yarington & Heatly, 1963; Adam & Brick, 1982).
2) META ANALYSIS

a) Howell et al (1992), analyzed reports concerning 361 patients with corrosive esophageal injury published in the English language literature since 1956 (10 retrospective and 3 prospective studies). No patients with first degree burns developed strictures. Of 228 patients with second or third degree burns treated with corticosteroids and antibiotics, 54 (24%) developed strictures. Of 25 patients with similar burn severity treated without steroids or antibiotics, 13 (52%) developed strictures (Howell et al, 1992).
b) Another meta-analysis of 10 studies found that in patients with second degree esophageal burns from caustics, the overall rate of stricture formation was 14.8% in patients who received corticosteroids compared with 36% in patients who did not receive corticosteroids (LoVecchio et al, 1996).
c) Another study combined results of 10 papers evaluating therapy for corrosive esophageal injury in humans published between January 1991 and June 2004. There were a total of 572 patients, all patients received corticosteroids in 6 studies, in 2 studies no patients received steroids, and in 2 studies, treatment with and without corticosteroids was compared. Of 109 patients with grade 2 esophageal burns who were treated with corticosteroids, 15 (13.8%) developed strictures, compared with 2 of 32 (6.3%) patients with second degree burns who did not receive steroids (Pelclova & Navratil, 2005).

3) Smaller studies have questioned the value of steroids (Ferguson et al, 1989; Anderson et al, 1990), thus they should be used with caution.
4) Ferguson et al (1989) retrospectively compared 10 patients who did not receive antibiotics or steroids with 31 patients who received both antibiotics and steroids in a study of caustic ingestion and found no difference in the incidence of esophageal stricture between the two groups (Ferguson et al, 1989).
5) A randomized, controlled, prospective clinical trial involving 60 children with lye or acid induced esophageal injury did not find an effect of corticosteroids on the incidence of stricture formation (Anderson et al, 1990).

a) These 60 children were among 131 patients who were managed and followed-up for ingestion of caustic material from 1971 through 1988; 88% of them were between 1 and 3 years old (Anderson et al, 1990).
b) All patients underwent rigid esophagoscopy after being randomized to receive either no steroids or a course consisting initially of intravenous prednisolone (2 milligrams/kilogram per day) followed by 2.5 milligrams/kilogram/day of oral prednisone for a total of 3 weeks prior to tapering and discontinuation (Anderson et al, 1990).
c) Six (19%), 15 (48%), and 10 (32%) of those in the treatment group had first, second and third degree esophageal burns, respectively. In contrast, 13 (45%), 5 (17%), and 11 (38%) of the control group had the same levels of injury (Anderson et al, 1990).
d) Ten (32%) of those receiving steroids and 11 (38%) of the control group developed strictures. Four (13%) of those receiving steroids and 7 (24%) of the control group required esophageal replacement. All but 1 of the 21 children who developed strictures had severe circumferential burns on initial esophagoscopy (Anderson et al, 1990).
e) Because of the small numbers of patients in this study, it lacked the power to reliably detect meaningful differences in outcome between the treatment groups (Anderson et al, 1990).

6) ADVERSE EFFECTS

a) The use of corticosteroids in the treatment of caustic ingestion in humans has been associated with gastric perforation (Cleveland et al, 1963) and fatal pulmonary embolism (Aceto et al, 1970).

H) SURGICAL PROCEDURE

1) SUMMARY: Initially if severe esophageal burns are found a string may be placed in the stomach to facilitate later dilation. Insertion of a specialized nasogastric tube after confirmation of a circumferential burn may prevent strictures. Dilation is indicated after 2 to 4 weeks if strictures are confirmed. If dilation is unsuccessful colonic intraposition or gastric tube placement may be needed. Early laparotomy should be considered in patients with evidence of severe esophageal or gastric burns on endoscopy.
2) STRING - If a second degree or circumferential burn of the esophagus is found a string may be placed in the stomach to avoid false channel and to provide a guide for later dilation procedures (Gandhi et al, 1989).
3) STENT - The insertion of a specialized nasogastric tube or stent immediately after endoscopically proven deep circumferential burns is preferred by some surgeons to prevent stricture formation (Mills et al, 1978; (Wijburg et al, 1985; Coln & Chang, 1986).

a) STUDY - In a study of 11 children with deep circumferential esophageal burns after caustic ingestion, insertion of a silicone rubber nasogastric tube for 5 to 6 weeks without steroids or antibiotics was associated with stricture formation in only one case (Wijburg et al, 1989).

4) DILATION - Dilation should be performed at 1 to 4 week intervals when stricture is present(Gundogdu et al, 1992). Repeated dilation may be required over many months to years in some patients. Successful dilation of gastric antral strictures has also been reported (Hogan & Polter, 1986; Treem et al, 1987).
5) COLONIC REPLACEMENT - Intraposition of colon may be necessary if dilation fails to provide an adequate sized esophagus (Chiene et al, 1974; Little et al, 1988; Huy & Celerier, 1988).
6) LAPAROTOMY/LAPAROSCOPY - Several authors advocate laparotomy or laparoscopy in patients with endoscopic evidence of severe esophageal or gastric burns to evaluate for the presence of transmural gastric or esophageal necrosis (Cattan et al, 2000; Estrera et al, 1986; Meredith et al, 1988; Wu & Lai, 1993).

a) STUDY - In a retrospective study of patients with extensive transmural esophageal necrosis after caustic ingestion, all 4 patients treated in the conventional manner (esophagoscopy, steroids, antibiotics, and repeated evaluation for the occurrence of esophagogastric necrosis and perforation) died while all 3 patients treated with early laparotomy and immediate esophagogastric resection survived (Estrera et al, 1986).

I) FOLLOW-UP VISIT

1) Obtain a follow-up esophagram and upper GI series to evaluate presence or absence of secondary scarring and/or stricture formation about 2 to 4 weeks following ingestion.
2) One 3-year-old child developed esophageal stricture 2 years after the acid ingestion in a prospective study of 41 patients. This child had a normal barium study at one year after ingestion (Zargar et al, 1989).

J) METHEMOGLOBINEMIA

1) SUMMARY

a) Determine the methemoglobin concentration and evaluate the patient for clinical effects of methemoglobinemia (ie, dyspnea, headache, fatigue, CNS depression, tachycardia, metabolic acidosis). Treat patients with symptomatic methemoglobinemia with methylene blue (this usually occurs at methemoglobin concentrations above 20% to 30%, but may occur at lower methemoglobin concentrations in patients with anemia, or underlying pulmonary or cardiovascular disorders). Administer oxygen while preparing for methylene blue therapy.

2) METHYLENE BLUE

a) INITIAL DOSE/ADULT OR CHILD: 1 mg/kg IV over 5 to 30 minutes; a repeat dose of up to 1 mg/kg may be given 1 hour after the first dose if methemoglobin levels remain greater than 30% or if signs and symptoms persist. NOTE: Methylene blue is available as follows: 50 mg/10 mL (5 mg/mL or 0.5% solution) single-dose ampules (Prod Info PROVAYBLUE(TM) intravenous injection, 2016) and 10 mg/1 mL (1% solution) vials (Prod Info methylene blue 1% intravenous injection, 2011). REPEAT DOSES: Additional doses may be required, especially for substances with prolonged absorption, slow elimination, or those that form metabolites that produce methemoglobin. NOTE: Large doses of methylene blue may cause methemoglobinemia or hemolysis (Howland, 2006). Improvement is usually noted shortly after administration if diagnosis is correct. Consider other diagnoses or treatment options if no improvement has been observed after several doses. If intravenous access cannot be established, methylene blue may also be given by intraosseous infusion. Methylene blue should not be given by subcutaneous or intrathecal injection (Prod Info methylene blue 1% intravenous injection, 2011; Herman et al, 1999). NEONATES: DOSE: 0.3 to 1 mg/kg (Hjelt et al, 1995).
b) CONTRAINDICATIONS: G-6-PD deficiency (methylene blue may cause hemolysis), known hypersensitivity to methylene blue, methemoglobin reductase deficiency (Shepherd & Keyes, 2004)
c) FAILURE: Failure of methylene blue therapy suggests: inadequate dose of methylene blue, inadequate decontamination, NADPH dependent methemoglobin reductase deficiency, hemoglobin M disease, sulfhemoglobinemia, or G-6-PD deficiency. Methylene blue is reduced by methemoglobin reductase and nicotinamide adenosine dinucleotide phosphate (NADPH) to leukomethylene blue. This in turn reduces methemoglobin. Red blood cells of patients with G-6-PD deficiency do not produce enough NADPH to convert methylene blue to leukomethylene blue (do Nascimento et al, 2008).
d) DRUG INTERACTION: Concomitant use of methylene blue with serotonergic drugs, including serotonin reuptake inhibitors (SRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), norepinephrine-dopamine reuptake inhibitors (NDRIs), triptans, and ergot alkaloids may increase the risk of potentially fatal serotonin syndrome (U.S. Food and Drug Administration, 2011; Stanford et al, 2010; Prod Info methylene blue 1% IV injection, 2011).

3) TOLUIDINE BLUE OR TOLONIUM CHLORIDE (GERMANY)

a) DOSE: 2 to 4 mg/kg intravenously over 5 minutes. Dose may be repeated in 30 minutes (Nemec, 2011; Lindenmann et al, 2006; Kiese et al, 1972).
b) SIDE EFFECTS: Hypotension with rapid intravenous administration. Vomiting, diarrhea, excessive sweating, hypotension, dysrhythmias, hemolysis, agranulocytosis and acute renal insufficiency after overdose (Dunipace et al, 1992; Hix & Wilson, 1987; Winek et al, 1969; Teunis et al, 1970; Marquez & Todd, 1959).
c) CONTRAINDICATIONS: G-6-PD deficiency; may cause hemolysis.

K) ACETYLCYSTEINE

1) N-acetylcysteine has been used in the treatment of potassium permanganate induced hepatotoxicity, but efficacy has not been established (Young et al, 1996).
2) Oral dosing regimen: 140 milligrams/kilogram loading dose followed by 70 milligrams/kilogram every 4 hours.
3) Intravenous regimen: 150 milligrams/kilogram NAC in 200 milliliters of D5W administered over 15 minutes followed by 50 milligrams/kilogram in 500 milliliters D5W infused over the next 4 hours. Finally, 100 milligrams/kilogram NAC in 1000 milliliters D5W is infused over the next 16 hour period.
4) Optimum duration of therapy has not been established.

L) ACUTE LUNG INJURY

1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).

3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).

M) CHELATION THERAPY

1) SUMMARY: Chelation with EDTA and sodium para-aminosalicylic acid has been used in patients with manganese intoxication. However, there is no experience with potassium permanganate exposure and the effectiveness of chelation treatment in improving existing neurological findings or preventing neurologic deterioration has not been clearly demonstrated.
2) Enhanced urinary excretion and mobilization of manganese from the blood and tissues occurs without restoring normal physiologic function. The efficacy of chelators is uncertain because the manganese body burden does not seem to correlate well to the clinical manifestations of manganese poisoning (Stokinger, 1981).
3) Chelation therapy may be effective early in the psychiatric phase of intoxication, before permanent neurological damage (Rodier, 1955). However, the effectiveness of chelation treatment in improving existing neurological findings or preventing neurologic deterioration has not been clearly demonstrated. A poor response has been seen in patients removed from long-term exposures (Cook et al, 1974).
4) CALCIUM TRISODIUM PENTETATE

a) Calcium trisodium pentetate was used to treat subacute potassium permanganate poisoning with associated neurologic toxicity in one patient. The authors report that manganese levels in urine increased and in serum decreased during calcium trisodium pentetate infusion. The administered dose was not specified (Holzgraefe et al, 1986).

5) SODIUM PARA-AMINOSALICYLIC ACID

a) SUMMARY: Sodium para-aminosalicylic acid has been associated with improvement in neurologic function in small numbers of patients with chronic manganese toxicity, but there have been no controlled studies.
b) CASE REPORT: After 21 years of occupational airborne exposure to manganese, a 50-year-old woman with symptoms of Parkinson disease (palpitation, hand tremor, lower limb myalgia, hypermyotonia, and a distinct fetinating gait) received 15 courses of p-aminosalicylic acid (6 grams/day IV drip infusion for 4 days and rested for 3 days). Her symptoms improved considerably, and improvement was maintained at 17 year follow up (Jiang et al, 2006).
c) CASE REPORTS: Two patients with chronic manganese poisoning were treated with intravenous sodium para-aminosalicylic acid (PAS), 6 g in 500 mL 10% glucose, administered as an infusion over 24 hours. PAS was administered daily for 4 days followed by a 3-day rest period. One patient was treated for 3.5 months; the duration of therapy in the other was not specified. Both patients demonstrated considerable improvement in neurologic function that was maintained on follow-up, 6 to 19 months later (Shuqin et al, 1992).

Eye Exposure

6.8.2)

A) INJURY OF GLOBE OF EYE

1) EVALUATION

a) ASSESSMENT CAUSTIC EYE BURNS: It may take 48 to 72 hours after the burn to assess correctly the degree of ocular damage (Brodovsky et al, 2000).
b) The 1965 Roper-Hall classification uses the size of the corneal epithelial defect, the degree of corneal opacification and extent of limbal ischemia to evaluate the extent of the chemical ocular injury (Brodovsky et al, 2000; Singh et al, 2013):

1) GRADE 1 (prognosis good): Corneal epithelial damage; no limbal ischemia.
2) GRADE 2 (prognosis good): Cornea hazy; iris details visible, ischemia less than one-third of limbus.
3) GRADE 3 (prognosis guarded): Total loss of corneal epithelium; stromal haze obscures iris details; ischemia of one-third to one-half of limbus.
4) GRADE 4 (prognosis poor): Cornea opaque; iris and pupil obscured, ischemia affects more than one-half of limbus.

c) A newer classification (Dua) is based on clock hour limbal involvement as well as a percentage of bulbar conjunctival involvement (Singh et al, 2013):

1) GRADE 1 (prognosis very good): 0 clock hour of limbal involvement and 0% conjunctival involvement.
2) GRADE 2 (prognosis good): Less than 3 clock hour of limbal involvement and less than 30% conjunctival involvement.
3) GRADE 3 (prognosis good): Greater than 3 and up to 6 clock hour of limbal involvement and greater than 30% to 50% conjunctival involvement.
4) GRADE 4 (prognosis good to guarded): Greater than 6 and up to 9 clock hour of limbal involvement and greater than 50% to 75% conjunctival involvement.
5) GRADE 5 (prognosis guarded to poor): Greater than 9 and less than 12 clock hour of limbal involvement and greater than 75% and less than 100% conjunctival involvement.
6) GRADE 6 (very poor): Total limbus (12 clock hour) involved and 100% conjunctival involvement.

2) MEDICAL FACILITY IRRIGATION

a) Begin irrigation immediately with copious amounts of water or sterile 0.9% saline, which ever is more rapidly available. Lactated Ringer's solution may also be effective. Once irrigation has begun, instill a drop of local anesthetic (eg, 0.5% proparacaine) for comfort; switching from water to slightly warmed sterile saline may also improve patient comfort (Singh et al, 2013; Spector & Fernandez, 2008; Ernst et al, 1998; Grant & Schuman, 1993). In one study, isotonic saline, lactated Ringer's solution, normal saline with bicarbonate, and balanced saline plus (BSS Plus) were compared and no difference in normalization of pH were found; however, BSS Plus was better tolerated and more comfortable (Fish & Davidson, 2010).

1) Continue irrigation for at least an hour or until the superior and inferior cul-de-sacs have returned to neutrality (check pH every 30 minutes), pH of 7.0 to 8.0, and remain so for 30 minutes after irrigation is discontinued (Spector & Fernandez, 2008; Brodovsky et al, 2000a). After severe alkaline burns, the pH of the conjunctival sac may only return to a pH of 8 or 8.5 even after extensive irrigation (Grant & Schuman, 1993). Irrigating volumes up to 20 L or more have been used to neutralize the pH (Singh et al, 2013; Fish & Davidson, 2010). Immediate and prolonged irrigation is associated with improved visual acuity, shorter hospital stay and fewer surgical interventions (Kuckelkorn et al, 1995; Saari et al, 1984).
2) Search the conjunctival sac for solid particles and remove them while continuing irrigation (Grant & Schuman, 1993).
3) For significant alkaline or concentrated acid burns with evidence of eye injury irrigation should be continued for at least 2 to 3 hours, potentially as long as 24 to 48 hours if pH not normalized, in an attempt to normalize the pH of the anterior chamber (Smilkstein & Fraunfelder, 2002). Emergent ophthalmologic consultation is needed in these cases (Spector & Fernandez, 2008).

3) MINOR INJURY

a) SUMMARY

1) If ocular damage is minor, artificial tears/lubricants, topical cycloplegics, and antibiotics may be all that are needed.

b) ARTIFICIAL TEARS

1) To promote re-epithelization, preservative-free artificial tears/lubricants (eg, hyaluronic acid hourly) may be used (Fish & Davidson, 2010; Tuft & Shortt, 2009).

c) TOPICAL CYCLOPLEGIC

1) Use to guard against development of posterior synechiae and ciliary spasm (Brodovsky et al, 2000b; Grant & Schuman, 1993). Cyclopentolate 0.5% or 1% eye drops may be administered 4 times daily to control pain (Tuft & Shortt, 2009; Spector & Fernandez, 2008).

d) TOPICAL ANTIBIOTICS

e) PAIN CONTROL

1) If pain control is required, oral or parenteral NSAIDs or narcotics are preferred to topical ocular anesthetics, which may cause local corneal epithelial damage if used repeatedly (Spector & Fernandez, 2008; Grant & Schuman, 1993). However, topical 0.5% proparacaine has been recommended (Spector & Fernandez, 2008).

4) SEVERE INJURY

a) SUMMARY

1) If the damage is minor, the above may be all that is needed. For grade 3 or 4 injuries, one or more of the following may be used, only with ophthalmologic consultation: acetazolamide, topical timolol, topical steroids, citrate, ascorbate, EDTA, cysteine, NAC, penicillamine, tetracycline, or soft contact lenses.

b) ARTIFICIAL TEARS

1) To promote re-epithelization, preservative-free artificial tears/lubricants (eg, hyaluronic acid hourly) may be used (Fish & Davidson, 2010; Tuft & Shortt, 2009).

c) PAIN CONTROL

d) CARBONIC ANHYDRASE INHIBITOR

1) Acetazolamide (250 mg orally 4 times daily) may be given to control increased intraocular pressure (Singh et al, 2013; Tuft & Shortt, 2009; Spector & Fernandez, 2008).

e) TOPICAL STEROIDS

1) DOSE: Dexamethasone 0.1% ointment 4 times daily to reduce inflammation. If persistent epithelial defect is present, discontinue dexamethasone by day 14 to reduce the risk of stromal melt (Tuft & Shortt, 2009). Other sources suggest that corticosteroids should be stopped if the epithelium has not covered surface defects by 5 to 7 days (Grant & Schuman, 1993a).
2) Topical prednisolone 0.5% has also been used. A further increase in corneoscleral melt may occur if topical steroids are used alone. In one study, topical prednisolone 0.5% was used in combination with topical ascorbate 10%; no increase in corneoscleral melt was observed when topical steroids were used until re-epithelization (Singh et al, 2013; Fish & Davidson, 2010).
3) In one retrospective study, fluorometholone 1% drops were administered every 2 hours initially, then decreased to four times daily when there was evidence of progressive corneal reepithelialization and lessened inflammation, and discontinued when corneal reepithelialization was complete (Brodovsky et al, 2000a).

a) STUDY: The combination of intensive topical corticosteroids, topical citrate and ascorbate, and oral citrate and ascorbate was associated with improved best corrected visual acuity and a trend towards more rapid corneal reepithelialization in Grade 3 alkali burns in one retrospective study (Brodovsky et al, 2000a).

f) ASCORBATE

1) Oral or topical ascorbate may be used to promote epithelial healing and reduce the risk of stromal necrosis (Fish & Davidson, 2010).
2) DOSE: Ascorbate 10% 4 times daily topically or 1 g orally (2 g/day) (Singh et al, 2013; Tuft & Shortt, 2009).
3) Ascorbate is needed for the formation of collagen and the concentration of ascorbate in the anterior chamber is decreased when the ciliary body is damaged by alkali burns (Tuft & Shortt, 2009; Grant & Schuman, 1993a). In one retrospective study, ascorbate drops (10%) were administered every 2 hours, then decreased to 4 times a day when there was evidence of progressive corneal reepithelialization and lessened inflammation, and discontinued when corneal reepithelialization was complete. These patients also received 500 mg of oral ascorbate 4 times daily, until discharge from the hospital (Brodovsky et al, 2000a).

g) CITRATE

1) Topical citrate may be used to promote epithelial healing and reduce the risk of stromal necrosis (Fish & Davidson, 2010).
2) DOSE: Potassium citrate 10% 4 times daily topically (Tuft & Shortt, 2009).
3) Citrate chelates calcium, and thereby interferes with the harmful effects of neutrophil accumulation, such as release of proteolytic enzymes and superoxide free radicals, phagocytosis and ulceration (Grant & Schuman, 1993a). In one retrospective study, 10% citrate drops were administered every 2 hours, then decreased to 4 times a day when there was evidence of progressive corneal reepithelialization and lessened inflammation, and discontinued when corneal reepithelialization was complete. These patients also received a urinary alkalinizer containing 720 mg of citric acid anhydrous and 630 mg of sodium citrate anhydrous 3 times daily, until discharge from the hospital (Brodovsky et al, 2000a).

h) COLLAGENASE INHIBITORS

1) Inhibitors of collagenase can inhibit collagenolytic activity, prevent stromal ulceration, and promote wound healing. Several effective agents, such as cysteine, n-acetylcysteine, sodium ethylenediamine tetra acetic acid (EDTA), calcium EDTA, penicillamine, and citrate, have been recommended (Singh et al, 2013; Tuft & Shortt, 2009; Perry et al, 1993; Seedor et al, 1987).
2) TETRACYCLINE: Has been found to have an anticollagenolytic effect. Systemic tetracycline 50 mg/kg/day reduced the incidence of alkali-induced corneal ulcerations in rabbits (Seedor et al, 1987).
3) DOXYCYCLINE: Decreased epithelial defects and collagenase activity in a rabbit model of alkali burns to the eye (Perry et al, 1993). DOSE: 100 mg twice daily (Tuft & Shortt, 2009).

i) ANTIBIOTICS

1) An antibiotic ophthalmic ointment or drops should be used for as long as epithelial defects persist (Brodovsky et al, 2000b; Grant & Schuman, 1993). Topical erythromycin or tetracycline ointment may be used (Spector & Fernandez, 2008). In patients with severe burns, a topical fluoroquinolone antibiotic drop 4 times daily may also be used (Tuft & Shortt, 2009). A topical fourth generation fluoroquinolone has been recommended as an antimicrobial prophylaxis in patients with large epithelial defect (Fish & Davidson, 2010).

j) TOPICAL CYCLOPLEGIC

1) Cyclopentolate 0.5% or 1% eye drops may be administered 4 times daily to control pain (Tuft & Shortt, 2009; Spector & Fernandez, 2008).

k) SOFT CONTACT LENSES

1) A bandage contact lens (eg, silicone hydrogel) may make the patient more comfortable and protect the surface (Fish & Davidson, 2010; Tuft & Shortt, 2009). Hydrophilic high oxygen permeability lenses are preferred (Singh et al, 2013). Soft lenses with intermediate water content and inherent rigidity may facilitate reepithelialization. The use of 0.5 normal sodium chloride drops hourly and artificial tears or lubricant eyedrops instilled 4 times a day may help maintain adequate hydration and lens mobility.

5) SURGICAL THERAPY

a) SURGICAL THERAPY CAUSTIC EYE INJURY

1) Early insertion of methylmethacrylate ring or suturing saran wrap over palpebral and cul-de-sac conjunctiva may prevent fibrinosis adhesions and reduce fibrotic contracture of conjunctiva, but the advantage of such treatments is not clear.
2) Limbal stem cell transplantation has been used successfully in both the acute stage of injury and the chronically scarred healing phase in patients with persistent epithelial defects after chemical burns (Azuara-Blanco et al, 1999; Morgan & Murray, 1996; Ronk et al, 1994).
3) In some patients, amniotic membrane transplantation (AMT) has been successful in improving corneal healing and visual acuity in patients with persistent epithelial defects after chemical burns. It can restore the conjunctival surface and decrease limbal stromal inflammation (Fish & Davidson, 2010; Sridhar et al, 2000; Su & Lin, 2000; Meller et al, 2000; Azuara-Blanco et al, 1999).
4) Control glaucoma. Remove any cataracts formed (Fish & Davidson, 2010; Tuft & Shortt, 2009).
5) In patients with severe injury, tenonplasty can be performed to promote epithelialization and prevent melting (Tuft & Shortt, 2009).
6) A keratoprosthesis placement has also been indicated in severe cases (Fish & Davidson, 2010). Penetrating keratoplasty is usually delayed as long as possible as results appear to be better with a greater lag time between injury and keratoplasty (Grant & Schuman, 1993).

B) IPRATROPIUM

1) CASE REPORT: A 45-year-old man sustained a splash contact in both eyes from a concentrated solution of potassium permanganate. Following ocular irrigation, a slit-lamp examination revealed the presence of foreign-body type irritation and the presence of several hard eroded lesions that appeared as granular deposits on the conjunctival tissue. The deposits were removed manually and a 5% ascorbic acid solution was used to irrigate the eyes and to dissolve the remaining granulated deposits. There was no residual damage from the treatment and the patient was released. No additional patient follow-up data were presented (Sigg et al, 1998).

C) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Dermal Exposure

6.9.1)

A) IRRIGATION

1) Remove contaminated clothing and jewelry and irrigate exposed areas with copious amounts of water. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Enhanced Elimination

1) It is unknown if hemodialysis would remove potassium permanganate. Dialysis should not be routinely recommended.

Abstracts

Range Of Toxicity

Summary

Minimum Lethal Exposure

1) The probable lethal dose for a 150 lb (70 kg) adult is 10 grams (approximately 1.5 teaspoons) (Pohanish, 2002; Ong et al, 1997; Middleton et al, 1990; Cowie & Escreet, 1981) .

a) Death may be delayed as much as 1 month after ingestion (HSDB, 2004).

1) ADULT

a) A 75-year-old man died after ingesting 20 grams of potassium permanganate. Complications included ARDS, hepatocellular injury, acute tubular necrosis, gastrointestinal burns, and hemorrhagic pancreatitis (Middleton et al, 1990).
b) A 24-year-old, Chinese woman died after intentional ingestion of an unknown amount of potassium permanganate crystals. She was admitted to the hospital with initial symptoms of brownish-black staining of the hands, lips, oropharynx, and upper esophagus, and swelling of the tongue, lips, and laryngeal structures. Between hours 36 and 72 hours after admission, she developed cardiovascular instability, disseminated intravascular coagulation, hepatic and renal failure, and adult respiratory distress syndrome. Progressive cardiovascular failure developed, and the patient died on day 6. Serum manganese levels on days 5 and 6 were 756 and 1629 mcmol/L, respectively (Ong et al, 1997; Young et al, 1996).

2) PEDIATRIC

a) A 33-month-old child died after ingesting one teaspoonful of potassium permanganate crystals (Justus & Gastmeier, 1967).
b) An 8-week-old child died following ingestion of an unknown amount of a approximately 0.01% potassium permanganate solution. Upon admission to the hospital, the infant presented with a swollen tongue, drooling, inflamed oral mucosa with brownish-black staining, and severe edema of the mouth, pharynx, and epiglottis. He died 28 hours later despite intensive support, having developed hypotension, metabolic acidosis, acute respiratory distress syndrome (ARDS), E. coli bacteremia, severe bradycardia, and cardiac arrest (Lifshitz et al, 1999).

Maximum Tolerated Exposure

1) ADULT

a) An 18-year-old man who ingested ten 300-mg tablets of potassium permanganate developed gastric burns complicated by gastric outlet obstruction 9 weeks after ingestion (Dagli et al, 1973).
b) A 66-year-old man ingested approximately 10 grams of potassium permanganate (approximately 125 mL of an 8% solution) over the course of a 4 week period, due to a dispensing error. He suffered severe abdominal pain and cramping, a reduction in physical capacity and ability to concentrate, visual disturbances, paresthesias of the right hand and foot, as well as increased sweating. Manganese in the blood was measured at a maximal level of 15 g/100 mL, and in the hair, 1.6 g/g. Nine months following the poisoning, the patient exhibited parkinsonian symptoms, including a resting tremor of four beats/second, a slow grade rigor of the extremities, and a shortening of gait (Holzgraefe et al, 1986).

1) A 14 year follow-up with the patient (then 80 years old) showed that most of the initial symptoms were improved, however, the parkinsonian syndrome was unchanged (Bleich et al, 1999).

c) A 42-year-old man developed caustic gastric injury about 12 hours after ingesting 20 g of a household antiseptic, containing potassium permanganate dissolved in 300 mL of water. Following supportive care, including IV fluids, a proton pump inhibitor, and antibiotics, his condition gradually improved and he was discharged 4 days later (Younan et al, 2013).

2) PEDIATRIC

a) A 3-year-old boy developed upper airway edema after ingesting an estimated 5 to 10 grams of potassium permanganate crystals. The child was treated with intubation, antibiotics, and corticosteroids. Liver and renal function tests remained normal and the child recovered completely (Southwood et al, 1987).

1) ADULT

a) In Sri Lanka, intentional ingestion of a laundry detergent containing a sachet each of 12.5 g oxalic acid and 1.2 g potassium permanganate resulted in 115 cases of toxicity with 18 fatalities. Gastrointestinal symptoms developed within 24 hours of ingestion. Of the individuals that ingested oxalic acid only, a case fatality ratio of 25.4% was observed, while a case fatality ratio of 9.8% occurred in patients ingesting both oxalic acid and potassium permanganate. Of the 35 patients who ingested 2 or mor sachets of both potassium permanganate and oxalic acid, 16 died (46%). Of the 58 patients who ingested one sachet or less, 2 died (3%). Most deaths occurred within one hour of ingestion. No deaths were reported in the potassium permanganate only ingestion. Individuals ingesting a sublethal dose of oxalic acid and potassium permanganate (n=51), developed acute renal failure 2 to 3 days after exposure. Median serum creatinine was 1.7 (Interquartile range: 0.91-4.4). Most recovered with supportive care (Gawarammana et al, 2009).

Serum Plasma Blood Concentrations

7.5.2)

A) TOXIC CONCENTRATION LEVELS

1) CASE REPORTS

a) A 3-year-old boy died after ingesting potassium permanganate solution (Gruz-Harday, 1967). Tissue manganese and potassium permanganate levels on autopsy were:

1) Intestines: manganese 15.7 milligrams/deciliter potassium permanganate 45.2 milligrams/deciliter
2) Liver: manganese 3.7 milligrams/deciliter potassium permanganate 10.66 milligrams/deciliter
3) Kidneys: manganese 1.01 milligrams/deciliter potassium permanganate 2.9 milligrams/deciliter
4) Brain: manganese 1.03 milligrams/deciliter potassium permanganate 2.97 milligrams/deciliter
5) Blood: manganese <0.025 milligrams/deciliter potassium permanganate <0.07 milligrams/deciliter
6) Urine: manganese <0.02 milligrams/deciliter potassium permanganate <0.06 milligrams/deciliter

Workplace Standards

1) Not Listed

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

1) Not Listed

Toxicity Information

7.7.1)

A) ANIMAL DATA

1) LD50- (ORAL)MOUSE:

a) 750 mg/kg (HSDB, 2004)

2) LD50- (ORAL)MOUSE:

a) 2157 mg/kg -- somnolence (general depressed activity) (RTECS, 2004)

3) LD50- (SUBCUTANEOUS)MOUSE:

a) 500 mg/kg (OHM/TADS, 2004; Lewis, 2000)

4) LD50- (ORAL)RAT:

a) 750 mg/kg (HSDB, 2004)

5) LD50- (ORAL)RAT:

a) 1090 mg/kg (RTECS, 2004)

B) HUMAN

Pharmacology Toxicology

Toxicologic Mechanism

1) Alkaline corrosives cause liquefaction necrosis, allowing deep penetration into mucosal tissue as cells are destroyed. Concentrated solutions of caustic materials can produce transmural necrosis with exposures as short as one second. Burns of the esophagus follow four distinct phases (Wolpowitz, 1974; Endicott, 1971).

a) INFLAMMATORY PHASE - lasts one or two days and demonstrates marked fibroblastic proliferation. Perforations may occur at this stage with resultant mediastinitis.
b) NECROTIC PHASE - occurs one to four days after injury. Cells die from coagulation of intracellular protein and inflammation of surrounding tissue develops. Vascular thrombosis and bacterial invasion worsen injury. Esophagoscopy is contraindicated as the esophagus is especially vulnerable to perforation.
c) GRANULATION PHASE - begins 3 to 5 days post injury when necrotic tissue sloughs. Granulation tissue begins to fill in tissue defects and connective tissue begins to form in 10 to 12 days.
d) CONSTRICTION PHASE - occurs 2 1/2 to 3 weeks following injury. Marked narrowing of the esophageal lumen may occur as the collagen fibers begin to contract.

2) MECHANISM OF OCULAR TOXICITY -

a) All alkalies saponify the fats in the cell membrane, destroying the cell.
b) The OH- ion reacts with collagen causing swelling, shortening and thickening of these fibrils.
c) If the ciliary body is penetrated, the aqueous humor is affected both quantitatively and qualitatively.
d) Aqueous and corneal stroma glucose is reduced, as is the ascorbate needed for collagen synthesis (Pfister & Patterson, 1977).
e) Collagen loss (corneal stromal ulceration) occurs 2 to 3 weeks after exposure.
f) Collagen becomes more susceptible to enzymatic degradation.

1) NEUROTOXICITY from manganese results from dopamine depletion and production of the neurotoxins dopamine quinone and hydrogen peroxide (Donaldson & Barbeau, 1985; Florence & Stauber, 1988).
2) BRAIN CHANGES are many, but include loss of nerve cells in the inner globus pallidus, diffuse degeneration of cells in the cerebral cortex, basal ganglia and cerebellum (Seth & Chandra, 1988). Some authors postulate that the neurologic features of manganism are mainly due to functional disturbances in striatal neurons (Wolters et al, 1989).

Physicochemical

Physical Characteristics

Molecular Weight

Other

1) Odorless (Lewis, 2001)

Animal Toxicology

References

General Bibliography

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POTASSIUM PERMANGANATE

Classification | Detailed evidence-based information

Therapeutic Toxic Class

Specific Substances

Available Forms Sources

Life Support

Clinical Effects

Laboratory Monitoring

Treatment Overview

Range Of Toxicity

Summary Of Exposure

Vital Signs

Heent

Cardiovascular

Respiratory

Neurologic

Gastrointestinal

Hepatic

Genitourinary

Acid-Base

Hematologic

Dermatologic

Endocrine

Reproductive

Carcinogenicity

Monitoring Parameters Levels

Radiographic Studies

Methods

Life Support

Patient Disposition

Monitoring

Oral Exposure

Eye Exposure

Dermal Exposure

Enhanced Elimination

Summary

Minimum Lethal Exposure

Maximum Tolerated Exposure

Serum Plasma Blood Concentrations

Workplace Standards

Toxicity Information

Toxicologic Mechanism

Physical Characteristics

Molecular Weight

Other

General Bibliography