Faculty Bibliography

Objective: Digoxin toxicity is determined largely by physical examination and electrocardiogram (ECG) findings; concentrations serve for confirmation. Some reports suggest decreased digoxin sensitivity in younger patients. We report a case of an infant with a very elevated digoxin concentration successfully managed conservatively. Case report: A 2-month-old boy (3.1 kg) with a past medical history of congestive heart failure was admitted to the hospital for vomiting and failure to thrive. The patient was started on oral digoxin, ordered as 0.015 mg twice daily. Due to a medication error, he was instead given 0.15mg twice a day for four days. His only other medication was furosemide. He had no new symptoms or change in the frequency of his vomiting. During a new medication reconciliation, the error was discovered. At that time, his vital signs were blood pressure 88/43mmHg, heart rate 123 beats/minute, respiratory rate 52, temperature 36.9 degreeC, and oxygen saturations 100% (on supplemental oxygen). His electrocardiogram (ECG) showed a sinus rhythm at 122 beats/minute with normal intervals. There was no evidence of increased automaticity or any arrhythmias. A serum digoxin concentration drawn 5 hours after his last dose was 16 nmol/L. Other laboratory findings at that time were notable for a potassium of 5.2mmol/L with slight hemolysis and a creatinine of 3.5 mumol/g. Repeat laboratory tests 8 hours after his last dose revealed a digoxin concentration of 15 nmol/L, potassium 5.3mmol/L (hemolyzed), creatinine 2.7 mumol/g and magnesium 0.72 mmol/L. He remained hemodynamically stable despite occasional episodes of vomiting. No cardiac ectopy or other events were noted. Oral digoxin was withheld and Digifab was not given. Repeat digoxin concentrations on day 1, 2, 4 and 5 were 9.6, 4.9, 2.9 and 1.92 nmol/L, respectively.
Conclusion(s): Digoxin toxicity often manifests with cardiac and constitutional symptoms. While toxicity is usually expected with elevated digoxin concentrations, only 63% of infants with a digoxin concentration greater than 6.4 nmol/L developed toxicity [1]. In fact, some evidence suggests that infants have decreased sensitivity to digoxin [2]. In this case the significantly elevated post-distribution digoxin concentration with no clear signs or symptoms of toxicity supports this presumption

Objective: Metaxalone is a central nervous system depressant utilized in the treatment of acute skeletal muscle pain. The exact mechanism of action has not been established but large ingestions have been associated with serotonin toxicity. We report on a patient who expired from complications of serotonin toxicity induced by massive metaxalone ingestion. Case report: A 20-year-old female with a prior history of depression presented to the emergency department unresponsive. History was unclear, however, her mother reported that the patient had access to her medications which included metaxalone, duloxetine, gabapentin, acetaminophen and oxycodone. She was intubated immediately and was found to be rigid with hyperreflexia and clonus. Initial vital signs were blood pressure 141/76 mmHg, heart rate 171 beats/minutes, respiratory rate 9/ minute, temperature 41.6 degreeC, oxygen saturations 98% (on supplemental oxygen). Initial venous blood gas showed pH 7.19, PCO2 23 mmHg, and lactate 1.2mmol/L. Initial blood tests revealed sodium 144mmol/L, potassium 2.6mmol/L, chloride 122mmol/L, bicarbonate 8 mmol/L, blood urea nitrogen 21mmol/L, creatinine 244 mumol/L, glucose 8.82 mmol/L and an acetaminophen concentration 662 mumol/L with an unknown time of ingestion. Despite supportive measures, external cooling, intravenous benzodiazepines and N-acetylcysteine therapy she developed multiorgan failure, cerebral edema and expired on day 3 of admission. High performance liquid chromatography/tandem mass spectrometry of admission blood samples revealed a serum metaxalone of 59 mg/dL (therapeutic less than 29.6 mg/dL) in addition to detectable dextromethorphan, diphenhydramine and gabapentin concentrations but no detectable serum duloxetine.
Conclusion(s): Metaxalone is an oxazolidinone analog which is a class that was initially developed as potential antidepressant (toloxatone) and antimicrobial agents (linezolid). Based on the structure, metaxalone is expected to have monoamine oxidase inhibitor activity and may cause serotonin toxicity by itself or in conjunction with additional serotonergic medications [1]. Here we present a severe case of serotonin toxicity associated with death of a young patient with confirmed elevated metaxalone concentrations