THE EFFECT OF THE N-METHYL-D-ASPARTATE RECEPTOR ANTAGONIST DEXTROMETHORPHAN ON PERIOPERATIVE BRAIN INJURY IN CHILDREN UNDERGOING CARDIAC-SURGERY WITH CARDIOPULMONARY BYPASS - RESULTS OF A PILOT-STUDY

Experimental evidence indicates a role of the N-methyl-D-aspartate rec eptor in the pathogenesis of brain injury occurring during cardiac sur gery with cardiopulmonary bypass (CPB). Dextromethorphan is a noncompe titive antagonist of this receptor with a favorable safety profile. Th irteen children age 3-36 months undergoing cardiac surgery with expect ed CPB of 60 minutes or more were randomly assigned to treatment with dextromethorphan (36-38 mg/kg/day) or placebo administered by naso-gas tric tube. Dextromethorphan was absorbed well and reached putative the rapeutic levels in blood and cerebrospinal fluid. Adverse effects were not observed. Mild hemiparesis developed after operation in one child of each group, and severe encephalopathy in one of the placebo group. Sharp waves were recorded in postoperative continuous electroencephal ography in all placebo (n = 7) but only in 2/6 dextromethorphan treate d children (p=0.02). Pre- and postoperative cranial magnetic resonance imaging (MRI) revealed less pronounced ventricular enlargement in the dextromethorphan group (not significant). An increase of periventricu lar white matter lesions was visible in two placebo-treated children o nly. No elevations of cerebrospinal fluid enzymes were observed in eit her group. Although children with dextromethorphan showed less abnorma lities in electroencephalography and MRI, dissimilarities of the treat ment groups by chance diminished conclusions to possible protective ef fects of dextromethorphan at this time.