Patients awaiting liver transplantation may suffer from severe hyponatremia. It has been suggested that hyponatremia or its treatment might be associated with central pontine myelinolysis (CPM), a serious complication that can be seen after orthotopic liver transplantation (OLT). We undertook this study to assess the outcome of hyponatremic patients after OLT and to evaluate the risk factors in the development of CPM. A total of 379 adult OLT performed in 347 patients between March 1993 and December 1995 was studied using a prospectively-collected data base and retrospective chart review. The following risk factors for the development of CPM were analyzed: primary liver disease, nutritional status, alcoholism, diuretic use, hepatic encephalopathy, United Network for Organ Sharing (UNOS) status, preoperative serum sodium, magnesium and cholesterol levels, increase in serum sodium concentration during surgery, and immunosuppressive treatment. Overall 12 patients (3.5%) underwent OLT in a hyponatremic state (serum sodium < or = 127 meq/L). At a median follow-up of 14 months, 8 patients were alive without any neurological sequel. Six of the 12 patients developed neurological complications in the early post-operative period including CPM in 3, confusion in 2, and seizure in 1. The 3 patients who developed CPM expired within 3 months of OLT. The changes in serum sodium concentration during OLT in patients with and without CPM were 20.7 +/- 8.1 and 7.0 +/- 5.1 meq/L, respectively (p = 0.005). No other risk factor could be identified in the development of CPM. It is concluded that prognosis of hyponatremic patients after OLT is poor if they develop CPM. Slow correction of hyponatremia perioperatively may be critical in preventing this devastating complication.