title: Influence of bupivacaine injection dose rate on cardiovascular depression, subsequent hemodynamic course, and related bupivacaine plasma levels in piglets.
abstract: OBJECTIVE
  Systemic local anesthetic (LA) toxicity resulting from inadvertent intravascular injection of LA is a rare but potentially fatal event. Early recognition of intravascular injection and approaches to improve therapeutic safety are required. This study investigated the influence of intravascular injection dose rate of bupivacaine on bupivacaine plasma levels and timing of LA-induced cardiovascular compromise.
  
  
  METHODS
  Forty-five piglets, anesthetized with sevoflurane, were randomized into three groups. Bupivacaine was intravenously infused at a rate of 1, 4, or 16 mg/kg/min (groups A, B, and C, respectively) until mean arterial pressure (MAP) dropped to 50% of initial value. Thereafter, bupivacaine infusion was stopped and spontaneous hemodynamic course was observed. Time to MAP 50%, amount of bupivacaine infused, bupivacaine plasma level at infusion stop, spontaneous survivors, or time from bupivacaine stop to circulatory arrest were recorded.
  
  
  RESULTS
  Median time to MAP 50% was 297, 119, and 65 s, respectively, in groups A, B, and C (P < 0.001). Median corresponding total amounts of bupivacaine infused were 5.0, 7.8, and 17.0 mg/kg (P < 0.01), and median bupivacaine plasma levels were 53.8, 180.0, and 439.8 μmol/l (P < 0.001). Five of 15 piglets in group A recovered spontaneously; in groups B and C, all animals died within 120 and 21 s, respectively.
  
  
  CONCLUSIONS
  Higher dose rates of bupivacaine showed much higher plasma bupivacaine levels related to absolute infused dose at MAP 50% and were associated with an increased mortality. Slow administration of LA is recommended to allow timely detection and stopping of inadvertent intravascular administration.
authors: Department of Anesthesia, University Children's Hospital Zurich, Zurich, Switzerland. jacqueline.mauch@ksa.ch
authors: Jacqueline
authors: J
authors: Mauch
authors: Annette P N
authors: AP
authors: Kutter
authors: Olga
authors: O
authors: Martin Jurado
authors: Nelly
authors: N
authors: Spielmann
authors: Mital H
authors: MH
authors: Dave
authors: Regula
authors: R
authors: Bettschart-Wolfensberger
authors: Markus
authors: M
authors: Weiss
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000097:blood* / Q000633:toxicity; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002045:Bupivacaine / Q000008:administration & dosage* / Q000097:blood* / Q000633:toxicity; D002319:Cardiovascular System / Q000187:drug effects*; D003864:Depression, Chemical; D004334:Drug Administration Schedule; D005260:Female; D006323:Heart Arrest / Q000097:blood / Q000139:chemically induced; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology; D011897:Random Allocation; D000077149:Sevoflurane; D013552:Swine
chemical_list: D000779:Anesthetics, Local; D008738:Methyl Ethers; D000077149:Sevoflurane; D002045:Bupivacaine