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Lipid Emulsion Infusion Rescues Dogs From Bupivacaine-Induced Cardiac Toxicity Weinberg et. al. Regional Anesthesia and Pain Medicine Vol 28, No 3 (May-June), 2003: pp 198-202 Overview Purpose:

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lipid emulsion infusion rescues dogs from bupivacaine induced cardiac toxicity

Lipid Emulsion Infusion Rescues Dogs From Bupivacaine-Induced Cardiac Toxicity

Weinberg et. al.

Regional Anesthesia and Pain Medicine

Vol 28, No 3 (May-June), 2003: pp 198-202

overview
Overview
  • Purpose:
    • author previously demonstrated encouraging results in resuscitation of severe bupivacaine cardiac toxicity in rats treated w/ IV lipid emulsion infusion.
    • Authors wanted to test hypothesis that Bupivacaine-induced cardiac toxicity in dogs (larger non-rodent mammals) could also be treated w/ lipid emulsion infusion.
overview3
Overview…
  • Methodology:
    • Bupivacaine 10 mg/kg IV over 10 sec.
    • Resuscitation
      • internal cardiac massage x 10 min
      • Either saline or 20% lipid infusion @ 4 mL/kg bolus then 0.5 mL/kg/min x 10 min
      • EKG, MAP, pHm, pmO2 monitored
overview4
Overview…
  • Significant findings:
    • Survival after 10 min unsuccessful cardiac massage
      • 100% for lipid treated dogs
      • 0% for saline treated dogs
    • Hemodynamics (PmO2, pHm)
      • Improved during resuscitation w/ lipids vs. saline
overview5
Overview…
  • Conclusion:
    • Infusing lipid emulsions during resuscitation from bupivacaine-induced cardiac toxicity substantially improved
      • Hemodynamics, pmO2, and pHm
    • Substantially increased survival in dogs.
authorship
Authorship
  • Guy Weinberg et al:
    • Department of Anesthesiology, University of Illinois at Chicago College of Medicine
    • Supported by Department of Anesthesiology at same school.
audience
Audience
  • Anesthesiologists and all MDs
impact
Impact
  • Increasing use of regional techniques
  • Bupivacaine-induced cardiac toxicity rare, but quite fatal
  • Could prove to be huge breakthrough
introduction
Introduction
  • Author clearly underlines significance of problem with opening statement:
    • “Bupivacaine overdose can lead to fatal cardiac toxicity in the form of severe arrhythmias and contractile dysfunction.”
    • Situates his own research by discussing his previous research on rats.
introduction10
Introduction…
  • Hypothesis clearly stated:
    • “We hypothesized that lipid infusion following bupivacaine treatment would improve recovery of cardiac function, hemodynamics, and myocaridal metabolism compared with saline-treated controls”.
methodology
Methodology
  • Approved by Institutional Animal Care Committee
  • 12 male non-purpose bread hounds (22-26 kg)
  • ? Randomly assigned to tmt vs. non-tmt arm
  • Non-blinded
methodology12
Methodology…
  • Instruments described:
    • Very detailed description of tissue probe
  • Anesthetic technique
    • 5 mg/kg propofol
    • Intubated ventilated w/ 1.5% Isoflurane + 30% O2
  • Details probe insertion, and surgical preparation of the animals etc.
methodology13
Methodology…
  • Details of bupivacaine overdose and subsequent resuscitation:
    • 10 mg/kg bupivacaine over 10 sec
    • Time of circulatory arrest noted (HR<10, MAP<30)
    • d/c Isoflurane and started 100% O2
    • Internal cardiac massage initiated x 10min
    • 4 mL/kg bolus (over 2 min) either saline or lipid emulsion
    • followed by continuous infusion 0.5 mL/kg/min x 10 min
methodology14
Methodology…
  • If NSR returned, internal cardiac massage continued until:
    • MAP>30mm Hg
  • 30 minute recovery measures recorded
  • All dogs sacrificed at the end.
methodology15
Methodology…
  • Statistics:
    • Statistical analysis tools used by author clearly identified in “statistics” subsection of Methods section.
results
Results…
  • Major findings presented clearly in results section:
    • Tables and graphs included
  • Findings address research objectives stated
discussion
Discussion
  • Results validate authors hypothesis
  • Limitations discussed:
    • Not blinded
      • But similar protocol before, during, after
      • No difference at baseline in hemodynamics, myocardial tissue measures
      • Difference not likely due to bias
      • Plus all dogs treated w/ lipid emulsion survived, and non treated w/ saline survived
    • When to start tmt
    • Dose of bupivacaine used
discussion18
Discussion…
  • Authors suggest further research in lipid based resuscitation for treatment of bupivacaine-induced cardiac toxicity:
    • Optimum dose
    • Dosage regimen
  • Risks of rapid lipid emulsion infusions need study too
discussion19
Discussion…
  • Suggestion of possible benefit of Propofol
    • Known to suppress bupivacaine-induced seizures
    • Commonly formulated in a 10% lipid emulsion vehicle
    • Theoretically could be used before severe hypotention/cardiac depression
    • Standard dose 2 mg/kg Propofol only provides 3% of dose of lipid in study
editorial by groban et al
Editorial by Groban et al
  • Recommendations:
    • Bupivacaine-induced toxicity:
      • When CNS hyperactivity doesn’t cease
        • Barbiturates, BZ or propofol
      • Standard ACLS 1st for cardiac arrest
        • Vassopressin over Epi (? Less drug induced VF, less acidosis)
        • Amiodarone over lido
      • Initiation of lipid infusion at earliest sign of severe LA cardiotoxicity (difficulty in tmt, good safety profile of lipids)
editorial by groban et al21
Editorial by Groban et al…
  • Recommendations:
    • Bupivacaine-induced toxicity:
      • If no lipid infusion available, and standard ACLS NOT working…try propofol
    • Animal experiments needed
    • Propofol as “antidote”
      • Tread w/ caution…negative ionotrope
    • Propofol for sedation in surgery under regional anesthesia may reduced susceptibility to LA-induced toxicity