Authors :
Presenting Author: Camila Gonzalez Aragon, MD – Nicklaus Children's Hospital
Marry Mack, PharmD BCPPS – Neurology Clinical Pharmacist, Clinical Pharmacy, Nicklaus Children's Hospital; Natanya Mishal, MD – Co-Medical Director of Inpatient Neurology, Brain Institute, Nicklaus Children's Hospital
Rationale:
Potassium bromide (KBr) is one of the oldest antiepileptics, with sedative and anticonvulsant properties by binding the gamma-aminobutyric acid receptor. Despite a narrow therapeutic index and side effect profile, its use has risen in refractory epilepsy.
Methods:
We reviewed the charts of patients on KBr therapy that presented with toxicity.
Results:
The first patient was a 19 year old female with intractable epilepsy secondary to SCN1A mutation related-Dravet syndrome who presented with decreased appetite and behavioral changes. She was on KBr (55 mg/kg/day) for a year. Laboratory examination showed hyperchloremia > 175 mmol/L and an anion gap of -63. KBr was stopped and she was managed with IV fluids with improvement of symptoms.
The second patient was a 19 year old female with intractable epilepsy secondary to SCN1A mutation related-Dravet syndrome who presented with drowsiness, and hallucinations, along with an acne-like rash. She was on KBr (20 mg/kg/day) for years. Laboratory examination showed hyperchloremia of 165 mmol/L and an anion gap of -51. KBr was discontinued and she was managed with IV fluis and diuretics. Behavioral changes and acne improved after weeks of discontinuing medication.
The third patient was a 16 year old female, with intractable epilepsy secondary to SCN1A mutation related-Dravet syndrome who presented with severe malnutrition, chronic diarrhea and weight loss (6 kg in 3 months). She was on KBr (15 mg/kg/day) for 5 years and tolerated it previously. Laboratory examination showed hyperchloremia of 153 mmol/L with an anion gap of –28. Esophagogastroduodenoscopy (EGD)/colonoscopy was only remarkable for gastric ulcers. She improved after she was weaned off KBr and treated with anti-acid medications and nutritional supplementation.
Conclusions:
Like our patient presentations, KBr toxicity can present in many ways. The most commonly described are: confusion, lethargy, ataxia, tremors, psychosis, delirium, gastric intolerance, anorexia, weight loss and skin lesions (Kodama, 2019). One of the most characteristic features of bromide therapy is pseudo-hyperchloremia with a negative anion gap. Bromide is a negatively charged anion that can interfere with chloride (Cl) level measurements, hence why on presentation patients have falsely elevated Cl levels with a negative anion gap. Bromide levels of about 5 mEq/L correspond to an additional 20 mmol/L of Cl ions (Chegondi, 2016).
KBr has high bioavailability, and its half-life is about nine to twelve days (with a median time to steady state of 28 days) therefore supportive treatment and hydration may be neccessary for a long period of time until Cl levels normalize and symptoms improve. Toxicity has been reported with low and high doses of treatment, with high and normal levels of bromide and after months or years of treatment; therefore clinicians should always be on the lookout for symptoms of bromide toxicity in all patients in KBr therapy.3
With the rising use of KBr, we have also seen a rise in its toxicity. With little pharmacokinetic data and varied presentations it is difficult to guide workup and management, therefore, we presented three cases of bromide toxicity to further characterize this entity.
Funding: N/A