Lipid Emulsion Infusion Rescues Dogs From Bupivacaine-Induced Cardiac Toxicity

1. 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

2. 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.

3. 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

4. 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

5. Overview… • Conclusion: • Infusing lipid emulsions during resuscitation from bupivacaine-induced cardiac toxicity substantially improved • Hemodynamics, pmO2, and pHm • Substantially increased survival in dogs.

6. Authorship • Guy Weinberg et al: • Department of Anesthesiology, University of Illinois at Chicago College of Medicine • Supported by Department of Anesthesiology at same school.

7. Audience • Anesthesiologists and all MDs

8. Impact • Increasing use of regional techniques • Bupivacaine-induced cardiac toxicity rare, but quite fatal • Could prove to be huge breakthrough

9. 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.

10. 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”.

11. 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

12. 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.

13. 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

14. Methodology… • If NSR returned, internal cardiac massage continued until: • MAP>30mm Hg • 30 minute recovery measures recorded • All dogs sacrificed at the end.

15. Methodology… • Statistics: • Statistical analysis tools used by author clearly identified in “statistics” subsection of Methods section.

16. Results… • Major findings presented clearly in results section: • Tables and graphs included • Findings address research objectives stated

17. 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

18. 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

19. 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

20. 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)

21. 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