title: [Bupivacaine toxicity and propofol anesthesia : animal study on intravascular bupivacaine injection].
abstract: BACKGROUND
  Several reports have confirmed the efficacy of Intralipid® (containing soya bean oil, egg phospholipids, glycerin and water) in the therapy of systemic local anesthetic intoxication. Pretreatment with Intralipid® shifted the dose-response to bupivacaine-induced asystole in rats. Whether intravenous anesthesia with propofol in the widely used medium chain triglyceride lipid emulsion increases the therapeutic range of systemically administered bupivacaine or not is unknown and was investigated in this study.
  
  
  METHODS
  A total of 30 piglets aged 2-6 weeks and weighing 4.5-6.5 kg were randomized into 2 groups and anesthetized with sevoflurane (group S) alone or with propofol 10 mg/kg body weight (BW)/h plus sevoflurane (group PS). After 60 min of steady state anesthesia arterial blood was sampled for assessment of blood gases, acid-base state and triglyceride plasma concentrations. Thereafter bupivacaine 0.125% was continuously infused by an infusion syringe pump through a central venous line at a rate of 4 mg/kg BW/min until invasively measured mean arterial pressure (MAP) was reduced by 50% of initial value. The bupivacaine infusion was stopped, blood for assessment of bupivacaine plasma concentration was drawn and the spontaneous hemodynamic course was observed. Resuscitation was not attempted. Results are presented as median and range. The Mann-Whitney U-test was used to assess differences between the two groups for triglyceride as well as for bupivacaine plasma concentrations measured at MAP 50%. A p-value≤0.05 was considered to be significant.
  
  
  RESULTS
  Baseline conditions (arterial blood pH, plasma protein and triglyceride plasma concentrations) did not differ significantly between the two groups. After 1 h of anesthesia, triglyceride plasma concentrations were significantly increased in group PS (median 0.69 mmol/l) compared to the corresponding baseline values (median 0.14 mmol/l; p<0.001) and to the 1 h values of group S (median 0.16 mmol/l; p<0.001). The total amount of bupivacaine administered was 9 mg/kg BW in both groups (6-13 mg/kg BW in group S, 5-13 mg/kg BW in group PS). Resulting bupivacaine plasma concentrations were 180 μmol/l (83-686 μmol/l) in group S and 185 μmol/l (130-465 μmol/l) in group PS. However, the total amount of bupivacaine administered and bupivacaine plasma concentrations at MAP 50% did not reveal statistically significant differences between the two groups but a huge variability of both parameters within each group was observed. None of the 30 piglets spontaneously recovered and they died from pulseless electrical activity or from asystolic cardiac arrest. The time from MAP 50% until cardiac arrest demonstrated a large variability but did not reveal significant differences between the two groups. The time to cardiac arrest was similar in both groups.
  
  
  CONCLUSIONS
  Medium/long chain triglyceride lipid emulsion (50:50) as widely used in propofol solutions did not increase therapeutic safety in cases of intravascular bupivacaine administration in this piglet model.
authors: Anästhesieabteilung, Universitäts-Kinderkliniken Zürich, Schweiz. jacqueline.mauch@ksa.ch
authors: J
authors: J
authors: Mauch
authors: A P N
authors: AP
authors: Kutter
authors: O
authors: O
authors: Martin Jurado
authors: N
authors: N
authors: Spielmann
authors: A
authors: A
authors: Frotzler
authors: R
authors: R
authors: Bettschart-Wolfensberger
authors: M
authors: M
authors: Weiss
mesh_terms: D000136:Acid-Base Equilibrium / Q000187:drug effects; D000771:Anesthesia, Intravenous; D018686:Anesthetics, Intravenous; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D002045:Bupivacaine / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005217:Fat Emulsions, Intravenous / Q000627:therapeutic use; D006863:Hydrogen-Ion Concentration; D007262:Infusions, Intravenous; D019300:Medical Errors; D015742:Propofol; D013552:Swine
chemical_list: D018686:Anesthetics, Intravenous; D000779:Anesthetics, Local; D005217:Fat Emulsions, Intravenous; D002045:Bupivacaine; D015742:Propofol