a) ONSET: The onset may be rapid and complete within 24 hours; it may be irreversible (Campbell, 2006). Onset of hearing loss occurred within 4 to 16 hours in adult patients (Tono et al, 1997)(Seung et al, 1980; (Oh et al, 1980) and within 7 days to 3 months in two children (Quick et al, 1975; Gradus et al, 1984).
b) INJURY SITE: The primary site of bromate-induced ototoxicity is the cochlea; the exact mechanism is unknown (Campbell, 2006).
c) DOSE: No data exists on the exact dose that causes injury (Campbell, 2006).
d) DURATION: Hearing or overt deafness may occur and it may be irreversible. This is more common in adults than in children.
e) INCIDENCE: Deafness is not a consistent finding in children, but it has a reported incidence of 85% in adults (Matsumoto et al, 1980).
f) CASE REPORT: Tinnitus and subsequent hearing loss occurred four hours after the deliberate ingestion of 7.5 g sodium bromate in a suicide attempt. The patient's hearing was permanently damaged (Wang et al, 1995).
g) CASE REPORT: A 48-year-old woman developed hearing loss after intentionally ingesting 300 mL of a permanent wave neutralizer that contained 6% sodium bromate. The hearing loss persisted despite hemodialysis and administration of 20 mL of 10% sodium thiosulfate. The patient was discharged approximately 45 days post-ingestion, continued on hemodialysis, and with persistent hearing loss (Sashiyama et al, 2002).

a) Hypotension is fairly common (Mack, 1988).

a) Myocarditis has been reported (Dunsky, 1947).

a) Respiratory depression may be noted (Mack, 1988).

a) Tachypnea may be noted (Mack, 1988).

a) Pulmonary edema may be noted (Mack, 1988).

a) Lethargy leading to coma may be noted (Mack, 1988; Parker & Barr, 1951).
b) CASE REPORT: Vomiting and coma immediately developed in a 25-day-old infant who was accidentally given approximately 1 oz of sodium bromate in her formula by an older sibling. Admission bromide concentration was 9800 mg/L. The infant died on hospital day 38 from anuric renal failure (Paloucek et al, 1997).

a) Seizures have occurred in cases involving acute renal failure (Dunsky, 1947; Thompson & Westfall, 1949; Gradus et al, 1984).

a) Delayed peripheral neuropathy, lasting 4 weeks, has been reported (Oh et al, 1980). A delayed sensation of burning of the feet has been reported to occur and persist for 1 to 2 months (Niwa et al, 1974).
b) CASE REPORT: Sensorimotor peripheral neuropathy, including prickling, tingling, and numbness in the feet, and hyporeflexia occurred seven days after the ingestion of 7.5 g sodium bromate in a suicide attempt. The patient recovered one year after the ingestion (Wang et al, 1995).
c) CASE REPORT: Peripheral neuropathy of the legs was reported in a 48-year-old woman approximately 5 weeks after intentionally ingesting 300 mL of a permanent wave neutralizer that contained 6% sodium bromate. The peripheral neuropathy spontaneously improved within 2 months after onset (Sashiyama et al, 2002).

a) CASE REPORT: A 17-year-old girl developed dizziness lasting for several days following an ingestion of a cup of hair neutralizer (approximately 20 g of sodium bromate) in a suicide attempt (Kutom et al, 1990).

a) Nausea, vomiting, and severe abdominal pain are presenting symptoms and occur about 1 to 2 hours after ingestion (Uchida et al, 2006; Sashiyama et al, 2002; Matsumoto et al, 1980; Kutom et al, 1990).
b) Long term gastrointestinal adverse sequelae are unlikely to accompany acute bromate poisoning (Mack, 1988).

a) Diarrhea may be a presenting symptom and occur 1.5 to 2 hours postingestion (Uchida et al, 2006; Matsumoto et al, 1980).

a) Hepatic edema has been reported (Dunsky, 1947).

a) Renal failure is a common manifestation of acute overdose. It usually develops insidiously over a period of 3 to 7 days and may be irreversible.
b) CASE REPORT: A 25-day-old infant ingested approximately 1 oz of sodium bromate in her formula given to her by an older sibling. Oliguria and an elevated creatinine developed in the first 24 hours. The infant died on hospital day 38 from anuric renal failure, despite peritoneal dialysis and sodium thiosulfate infusions (other extracorporeal treatments were not considered based on the infants size) (Paloucek et al, 1997).
c) CASE REPORT: Wang et al (1995) reported a case of a 25-year-old woman ingesting 7.5 g sodium bromate in a suicide attempt. Two days later, the patient developed proteinuria followed by acute oliguric renal failure. Renal function improved after management by hemodialysis (Wang et al, 1995).
d) CASE REPORT: A 78-year-old woman developed severe acute renal failure (BUN 18.7 mg/dL [6.7 mmol/L]; creatinine 1.0 mg/dL [88.4 mcmol/L]) after the accidental ingestion of a cup of permanent hair waving solution containing 7% sodium bromate. Following treatment with hemodialysis (from day 2 for 3 days) and hemodiafiltration (from day 6 for 3 more days), her renal function recovered. A percutaneous renal biopsy on day 21 showed degeneration of renal tubules and mild interstitial edema; however, some regeneration of tubular epithelium was also observed. The glomerulus exhibited minor changes with a mild thickening of Bowman's capsule. In some tubular epithelial cells, damage to mitochondria and lysosomes was still evident on electron microscopy. She was discharged on day 34 without any CNS or auditory disturbances (Uchida et al, 2006).
e) CASE REPORT: A 48-year-old woman developed acute renal failure and hearing loss after intentionally ingesting 300 mL of a permanent wave neutralizer that contained 6% sodium bromate. The patient was anuric and laboratory analysis indicated elevated serum creatinine and BUN concentrations (5.8 mg/dL and 33.1 mg/dL, respectively). Following several sessions of hemodialysis, there was a small urine output; however, her serum creatinine concentration increased to 8.3 mg/dL and maintenance hemodialysis of 3 times per week was required (Sashiyama et al, 2002).

a) Acetonuria, albuminuria, and hematuria may be noted (Kutom et al, 1990).

a) INTERSTITIAL FIBROSIS: Later stages of renal failure reveal sclerosis of the glomeruli and interstitial fibrosis (Kurokawa et al, 1990).

a) Metabolic acidosis has been described in conjunction with acute renal failure (Warshaw et al, 1985; Kitto & Dumars, 1949; Gradus et al, 1984; Lue et al, 1988).

a) CASE REPORT: Hemolysis and thrombocytopenia were described in a 17-month-old child following bromate ingestion (Gradus et al, 1984).
b) CASE REPORT: A 48-year-old woman intentionally ingested 300 mL of a permanent wave neutralizer (containing 6% sodium bromate) and developed severe anemia 2 weeks later. The patient's LDH concentration was also elevated at 1,792 international units/L, suggesting the occurrence of hemolytic anemia. With supportive care, the patient's anemia resolved (Sashiyama et al, 2002).

a) Anemia or decreased hemoglobin has been described (Warshaw et al, 1985; Dunsky, 1947; Thompson & Westfall, 1949; Kitto & Dumars, 1949).

a) Listed as: Potassium bromate
b) Carcinogen Rating: 2B

a) Obtain audiograms as necessary to assess ototoxicity.

a) Immediate stomach neutralization with sodium bicarbonate dissolved in water may prevent formation of hydrobromic acid, which is responsible for gastrointestinal irritant effects; however information on efficacy and safety of this recommendation is anecdotal (Thompson & Westfall, 1949); it is NOT routinely recommended.

a) Patients with mild to moderate bromate toxicity may only require symptomatic and supportive care. Treat gastrointestinal toxicity with IV fluid hydration and antiemetics. Patients with ototoxicity should be evaluated with audiologic studies.

a) Treat hypotension with IV fluids, followed by vasopressors as needed. Treat seizures with benzodiazepines as needed. Respiratory depression and CNS depression may require intubation. Renal replacement therapy may be required for oliguric renal failure. Rarely, hemolysis may require a transfusion of packed red blood cells.

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.

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).

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

a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).

a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2010; Chin et al, 2008).

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):

a) Blood bromine levels of 75 milligrams percent were reported in an 8-year-old boy after ingestion of 2 ounces of cold wave neutralizer (Kitto & Dumars, 1949).
b) A serum bromide level of 9800 milligrams/liter was reported in a 25-day-old infant following an ingestion of about one ounce of sodium bromate from a hair neutralizer solution. The infant died 38 days later (Paloucek et al, 1997).
c) A blood bromine concentration of 99.3 mg/L was reported in a 48-year-old woman who intentionally ingested 300 mL of a permanent wave neutralizer that contained 6% sodium bromate (Sashiyama et al, 2002).