Previous studies have demonstrated that
bupivacaine administered directly into the central nervous system (CNS) is capable of producing signs of
bupivacaine cardiovascular toxicity. To investigate the mechanisms by which
bupivacaine may act within the CNS to produce cardiovascular toxicity, we studied four groups of
halothane-anesthetized rabbits in which infusion of intracerebroventricular (icv)
bupivacaine or intravenous (iv)
phenylephrine resulted in dysrhythmias and
hypertension. In group 1 (n = 5), icv
bupivacaine (500 +/- 79 micrograms [mean +/- SEM]) produced dysrhythmias lasting 73 +/- 13 min, whereas icv saline caused no dysrhythmias or
hypertension. In group 2 (n = 9), icv
bupivacaine-induced
hypertension and dysrhythmias were abolished by icv
midazolam in 4.4 +/- 0.6 min, and when dysrhythmias and
hypertension recurred (22 +/- 0.9 min),
hexamethonium (10 mg/kg iv) promptly terminated dysrhythmias and
hypertension (14 +/- 1 s). In group 3 (n = 10), icv
bupivacaine-induced dysrhythmias and
hypertension were not affected by increasing the inspired
halothane concentration from 0.8 to 1.6%. In group 4 (n = 6), iv
phenylephrine-induced dysrhythmias and
hypertension were not affected by icv
midazolam. These results suggest that icv
bupivacaine produces dysrhythmias and
hypertension by increasing autonomic nervous system (ANS) outflow from the brain stem. The finding that peripheral autonomic blockade by
hexamethonium rapidly terminated dysrhythmias and
hypertension supports this mechanism. We speculate that icv
bupivacaine produces an increase in autonomic outflow by blockade of the inhibitory
gamma-aminobutyric acid (GABA) neurons that are known to be the principal tonic inhibitors of the ANS.(ABSTRACT TRUNCATED AT 250 WORDS)