BUPIVACAINE PLASMA-CONCENTRATIONS ASSOCIA TED WITH CLINICAL AND ELECTROENCEPHALOGRAPHIC SIGNS OF EARLY CENTRAL-NERVOUS-SYSTEM TOXICITY IN INFANTS DURING AWAKE CAUDAL ANESTHESIA

In order to evaluate whether caudal bupivacaine 3.1 mg/kg is associate d with early central nervous system toxicity in awake infants, a clini cal trial was performed. Methods: After obtaining Local Ethical Commit tee approval and informed parental consent, seven awake infants (postc onceptual age: 36-52 wks; weight: 2.2-4.7 kg) received a caudal block with bupivacaine 3.1 mg/kg with epinephrine 5 ug/ml in the left latera l position. Before performance of the caudal block a five minute EEG r egistration was performed, immediately followed by an assessment of th e patient's clinical status based on a scoring system of following par ameters: level of consciousness; muscular tone in upper extremities, t ested by flexion and extension of the elbows; and the quality of the p atient's cry in response to a skin pinch. Twenty minutes after the cau dal block another EEG was performed and another assessment of the clin ical status of the patient. After completion of the clinical assessmen t blood samples were collected for determination of plasma bupivacaine ,albumin and alpha-1 acid glycoprotein concentrations. Results:ln six of seven infants the EEG pat tern from the first to the second recordi ng showed a shift of the general frequency spectrum towards a lower ra nge. In two of these patients (No. 3 and 4) signs of pharmacologically induced antiepileptic effects (disappereance of sharp waves) were obs erved. Patients No. 2 and 6 showed signs of increased muscular activit y and of suspect epileptic activity. Bupivacaine plasma concentrations ranged from 0.56-1.62 ug/ml,alpha-l acid glycoprotein levels from 0.3 3-0.76 g/l and albumin levels from 25-38 g/l. Discussion: In a few pat ients this systemic effect was clinically also associated with what is usually classified as early central nervous system toxicity. As a res ult of these findings the study was stopped prematurely, due to safety reasons. The low plasma levels of bupivacaine associated with side ef fects in this study may have two possible explanations. First, our pat ients did not receive any sedative drugs or anaesthetics that could ha ve masked symptoms or have increased the threshold for systemic effect s. Second, as can be expected in this age group plasma levels of alpha -1 acidglycoprotein were low. Thus, the lower plasma concentrations of total bupivacaine observed in the present study might have been assoc iated with a similar unbound, free concentration of bupivacaine as it is seen in older children and adults at total plasma levels of 2-4 ug/ ml and at alpha-1 acidglycoprotein levels within the normal adult rang e. We conclude that Bupivacaine at 3 mg/kg is associated with systemic side effects in infants receiving awake caudal anaesthesia. Therefore we recommend to aim at a dose of not larger than 2 mg/kg in caudal bl ocks if no premedication or other sedative drugs are given simultaneou sly.