title: [Early signs of toxicity and "subtoxic" conditions in infant monitoring. Bupivacaine plasma levels following caudal anesthesia].
abstract: In order to evaluate whether caudal bupivacaine 3.1 mg/kg is associated with early central nervous system toxicity in awake infants, a clinical trial was performed.
  
  
  METHODS
  After obtaining Local Ethical Committee approval and informed parental consent, seven awake infants (postconceptual 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 lateral position. Before performance of the caudal block a five minute EEG registration was performed, immediately followed by an assessment of the patient's clinical status based on a scoring system of following parameters: level of consciousness; muscular tone in upper extremities, tested by flexion and extension of the elbows; and the quality of the patient's cry in response to a skin pinch. Twenty minutes after the caudal block another EEG was performed and another assessment of the clinical status of the patient. After completion of the clinical assessment blood samples were collected for determination of plasma bupivacaine, albumin and alpha-1 acid glycoprotein concentrations.
  
  
  RESULTS
  In six of seven infants the EEG pattern from the first to the second recording showed a shift of the general frequency spectrum towards a lower range. In two of these patients (No. 3 and 4) signs of pharmacologically induced antiepileptic effects (disappearance of sharp waves) were observed. Patients No. 2 and 6 showed signs of increased muscular activity and of suspect epileptic activity. Bupivacaine plasma concentrations ranged from 0.56-1.62 ug/ml, alpha-1 acid glycoprotein levels from 0.33-0.76 g/l and albumin levels from 25-38 g/l.
  
  
  CONCLUSIONS
  In a few patients this systemic effect was clinically also associated with what is usually classified as early central nervous system toxicity. As a result of these findings the study was stopped prematurely, due to safety reasons. The low plasma levels of bupivacaine associated with side effects in this study may have two possible explanations. First, our patients did not receive any sedative drugs or anaesthetics that could have masked symptoms or have increased the threshold for systemic effects. 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 associated 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 range. 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 blocks if no premedication or other sedative drugs are given simultaneously.
authors.affiliation: Abteilung für Anästhesie, LKH Klagenfurt.
authors.forename: C
authors.initials: C
authors.lastname: Breschan
authors.forename: E
authors.initials: E
authors.lastname: Hellstrand
authors.forename: R
authors.initials: R
authors.lastname: Likar
authors.forename: P A
authors.initials: PA
authors.lastname: Lönnquist
mesh_terms: D000775:Anesthesia, Spinal; D000779:Anesthetics, Local / Q000009:adverse effects / Q000097:blood; D002045:Bupivacaine / Q000009:adverse effects / Q000097:blood; D003448:Crying; D004569:Electroencephalography / Q000187:drug effects; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D007223:Infant; D016343:Monitoring, Intraoperative; D012709:Serum Albumin / Q000378:metabolism
chemical_list: D000779:Anesthetics, Local; D006023:Glycoproteins; D012709:Serum Albumin; D002045:Bupivacaine
vernacular_title: Toxizität und "subtoxische" Frühzeichen im Wachzustand bei Säuglingen. Bupivacainplasmaspiegel nach Kaudalanästhesien.