Rhabdomyolysis and elevated liver enzymes after rapid correction of hyponatremia due to pneumonia and concurrent use of aripiprazole: A case report

To the Editor

Rhabdomyolysis has been reported with rapid correction of hyponatremia, while liver aminotransferase abnormalities are rare. We report the first case of rhabdomyolysis and elevated liver enzymes after rapid correction of hyponatremia due to pneumonia and concurrent use of aripiprazole.

A 54-year-old Chinese patient with schizophrenia was admitted to the emergency room due to cough, expectoration and seizures. Further diagnostic tests revealed severe hyponatremia (sodium 118.0 mmol/L) and pneumonia. Correcting hyponatraemia was first attempted with hypertonic saline. Meanwhile, cefoperazone–tazobactam was added and antipsychotics (clozapine 100 mg/day and aripiprazole 30 mg/day) were discontinued. In the first 10 hours after admission, a higher than expected increase in sodium (22 mmol/L) was noted, and sodium correction was then suspended. Although the sodium level returned to normal, his serum creatine kinase (CK) level increased to 22 862 U/L and then increased progressively to reach a peak level of 23 674 U/L (day 4). His aspartate transaminase (AST) and alanine aminotransferase (ALT) levels also increased from 44 U/L to a peak value of 531 U/L (day 1) and 36 U/L to a peak value of 158 U/L (day 6), respectively. His CK, AST and ALT levels gradually returned to normal following hepatoprotective Wuzhi tablet (Schisandra sphenanthera extract) and high-volume alkaline diuresis treatment under the close monitoring of serum sodium.

Our patient had seizures due to hyponatremia, which was attributed to the syndrome of inappropriate antidiuretic hormone (SIADH). SIADH may have been a consequence of both the pneumonia and the serotonin-mediated effects of aripiprazole (Yam et al., 2013). Although it is not possible to exclude the role of seizures, the timing and the extent of CK elevation highly suggested that correcting hyponatremia rapidly was the main cause of rhabdomyolysis. Antipsychotics could also be important confounding factors by increasing amounts of serotonin, itself toxic to skeletal muscles, through blockade of 5-HT_2A receptors (Tseng and Hwang, 2009). The delayed peak in CK level of 4 days after admission could be partly explained by the long elimination half-life of aripiprazole (75–146 hours). Liver aminotransferase abnormalities, particularly AST, were also observed, and his AST level changed in concert with CK level, suggesting that skeletal muscle may be a significant source of AST elevation (Weibrecht et al., 2010).

In conclusion, hyponatremia may arise during aripiprazole treatment in the context of known risk factors (i.e. pneumonia). When correcting hyponatremia, monitoring muscle and liver enzyme levels routinely is advised.