Skip to main content
SpringerLink
Log in

Effects of Remifentanil Pretreatment on Bupivacaine Cardiotoxicity in Rats

Cardiovascular Toxicology volume 18, pages 56–62 (2018)Cite this article

Abstract

Unintentional intravascular administration of bupivacaine may cause local anesthetic systemic toxicity (LAST). Although many systems are affected in LAST, the cardiovascular effects can be life-threatening. Remifentanil is a selective, ultra-short-acting, µ-opioid receptor agonist opioid. This study assessed the effects of combined pretreatment with intravenous lipid emulsion (ILE) and remifentanil on the cardiotoxicity caused by bupivacaine in an experimental model of anesthetized rats. The rats were divided into three groups. Group B received a saline pretreatment plus a bupivacaine, group L received ILE pretreatment plus a bupivacaine, and in group R, remifentanil was infused intravenously, plus ILE pretreatment plus a bupivacaine. The electrocardiogram tracing, invasive arterial pressure, and heart rate (HR) of rats were monitored continuously. Arterial blood gas analysis was performed in all groups. Arterial blood gas analysis revealed that the baseline pH (7.38 ± 0.31, 7.39 ± 0.41, and 7.37 ± 0.02 for groups B, L, and R, respectively), PaO2 (198.5 ± 9.45, 196.1 ± 32.3, and 197.7 ± 9.25 mmHg, respectively), and PaCO2 (37.8 ± 4.91, 37.4 ± 4.85, and 36.9 ± 4.42 mmHg, respectively) were similar in the groups (p > 0.05). Time to first alteration in QRS complex, time to first arrhythmia, time to 25, 50, and 75% reductions in HR, time to 25, 50, and 75% reductions in MAP, and time to asystole were recorded. Widening of the QRS complex was found 41.8 ± 16.6, 88.5 ± 7.91, and 103.0 ± 15.7 s after initiating the bupivacaine infusion in groups B, L, and R, respectively. Time elapsed until 25% reduction in HR was found 136.5 ± 50.7, 284.7 ± 31.7, and 292.0 ± 46.0 s for groups B, L, and R, respectively, and that until 25% reduction in MAP was found 101.7 ± 14.3, 245.0 ± 36.6, and 237.6 ± 52.6 s, respectively. Arrhythmia was observed after 135.2 ± 27.4, 172.4 ± 18.1, and 176.2 ± 23.0 s in groups B, L, and R, respectively. Finally, asystole occurred after 553.6 ± 74.4, 766.7 ± 64.8, and 800.1 ± 94.7 s in groups B, L, and R, respectively. This finding indicates that the survival time of rats administered pretreatment with ILE plus remifentanil and those given ILE was observed to be longer. Additionally, this study found that intravenous lipid emulsion plus remifentanil pretreatment did not result in better durations in terms of formation of bupivacaine intoxication and asystole compared to lipid pretreatment alone.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3

References

  1. Groban, L. (2003). Central nervous system and cardiac effects from long-acting amide local anesthetic toxicity in the intact animal model. Regional Anesthesia and Pain Medicine, 28, 3–11.

    Article  CAS  PubMed  Google Scholar 

  2. Clarkson, C. W., & Hondeghem, L. M. (1985). Mechanism for bupivacaine depression of cardiac conduction: fast block of sodium channels during the action potential with slow recovery from block during diastole. Anesthesiology, 62, 396–405.

    Article  CAS  PubMed  Google Scholar 

  3. Litz, R. J., Roessel, T., Heller, A. R., & Stehr, S. N. (2008). Reversal of central nervous system and cardiac toxicity after local anesthetic intoxication by lipid emulsion injection. Anesthesia and Analgesia, 106, 1575–1577.

    Article  PubMed  Google Scholar 

  4. Oda, Y., & Ikeda, Y. (2013). Effect of lipid emulsion on the central nervous system and cardiac toxicity of bupivacaine and levobupivacaine in awake rats. Journal of Anesthesia, 27, 500–504.

    Article  PubMed  Google Scholar 

  5. Shirole, R. L., Shirole, N. L., & Saraf, M. N. (2015). In vitro relaxant and spasmolytic effects of essential oil of Pistacia integerrima Stewart ex Brandis Galls. Journal of Ethnopharmacology, 168, 61–65.

    Article  CAS  PubMed  Google Scholar 

  6. Nita, I. I., Hershfinkel, M., Lewis, E. C., & Sekler, I. (2015). A crosstalk between Na+ channels, Na+/K+ pump and mitochondrial Na+ transporters controls glucose-dependent cytosolic and mitochondrial Na+ signals. Cell Calcium, 57, 69–75.

    Article  CAS  PubMed  Google Scholar 

  7. Lynch, C., 3rd. (1986). Depression of myocardial contractility in vitro by bupivacaine, etidocaine, and lidocaine. Anesthesia and Analgesia, 65, 551–559.

    CAS  PubMed  Google Scholar 

  8. Weinberg, G. L., VadeBoncouer, T., Ramaraju, G. A., Garcia-Amaro, M. F., & Cwik, M. J. (1998). Pretreatment or resuscitation with a lipid infusion shifts the dose–response to bupivacaine-induced asystole in rats. Anesthesiology, 88, 1071–1075.

    Article  CAS  PubMed  Google Scholar 

  9. Rosenblatt, M. A., Abel, M., Fischer, G. W., Itzkovich, C. J., & Eisenkraft, J. B. (2006). Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest. Anesthesiology, 105, 217–218.

    Article  PubMed  Google Scholar 

  10. ACMT. (2011). ACMT position statement: Interim guidance for the use of lipid resuscitation therapy. Journal of Medical Toxicology, 7(1), 81–82.

    Article  Google Scholar 

  11. ASRA Checklist for treatment of local anesthetic systematic toxicity 2011Availlable from:https://www.asra.com/advisory-guidelines/article/3/checklist-for-treatment-of-local-anesthetic-systemic-toxicity. Accessed 29 December 2016.

  12. Hayes, B. D., Gosselin, S., Calello, D. P., Nacca, N., Rollins, C. J., Abourbih, D., et al. (2016). Systematic review of clinical adverse events reported after acute intravenous lipid emulsion administration. Clinical Toxicology (Phila), 54, 365–404.

    Article  CAS  Google Scholar 

  13. Hoegberg, L. C. G., Bania, T. C., Lavergne, V., Bailey, B., Turgeon, A. F., Thomas, S. H. L., et al. (2016). Systematic review of the effect of intravenous lipid emulsion therapy for local anesthetic toxicity. Clinical Toxicology (Phila), 54, 167–193.

    Article  CAS  Google Scholar 

  14. Patel, S. S., & Spencer, C. M. (1996). Remifentanil. Drugs, 52, 417–427.

    Article  CAS  PubMed  Google Scholar 

  15. Peart, J. N., Gross, E. R., & Gross, G. J. (2005). Opioid-induced preconditioning: Recent advances and future perspectives. Vascular Pharmacology, 42, 211–218.

    Article  CAS  PubMed  Google Scholar 

  16. Yu, C. K., Li, Y. H., Wong, G. T., Wong, T. M., & Irwin, M. G. (2007). Remifentanil preconditioning confers delayed cardioprotection in the rat. British Journal of Anaesthesia, 99, 632–638.

    Article  CAS  PubMed  Google Scholar 

  17. Zhang, Y., Chen, Z.-W., Girwin, M., & Wong, T.-M. (2005). Remifentanil mimics cardioprotective effect of ischemic preconditioning via protein kinase C activation in open chest of rats. Acta Pharmacologica Sinica, 26, 546–550.

    Article  CAS  PubMed  Google Scholar 

  18. Hanci, V., Karakaya, K., Yurtlu, S., Hakimoglu, S., Can, M., Ayoglu, H., et al. (2009). Effects of dexmedetomidine pretreatment on bupivacaine cardiotoxicity in rats. Regional Anesthesia and Pain Medicine, 34, 565–568.

    Article  CAS  PubMed  Google Scholar 

  19. Yurtlu, D. A., & Kaya, K. (2013). Ropivacaine, articaine or combination of ropivacaine and articaine for epidural anesthesia in cesarean section: A randomized, prospective, double-blinded study. Brazilian Journal of Anesthesiology, 63, 85–91.

    Article  PubMed  Google Scholar 

  20. Faccenda, K. A., & Finucane, B. T. (2001). Complications of regional anaesthesia Incidence and prevention. Drug Safety, 24, 413–442.

    Article  CAS  PubMed  Google Scholar 

  21. Felice, K., & Schumann, H. (2008). Intravenous lipid emulsion for local anesthetic toxicity: A review of the literature. Journal of Medical Toxicology, 4, 184–191.

    Article  PubMed  PubMed Central  Google Scholar 

  22. de La Coussaye, J. E., Eledjam, J. J., Brugada, J., & Sassine, A. (1993). Cardiotoxicity of local anesthetics. Cahiers d’Anesthesiologie, 41, 589–598.

    Google Scholar 

  23. Cave, G., Harvey, M., Willers, J., Uncles, D., Meek, T., Picard, J., et al. (2014). LIPAEMIC report: Results of clinical use of intravenous lipid emulsion in drug toxicity reported to an online lipid registry. Journal of Medical Toxicology, 10, 133–142.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Neal, J. M., Bernards, C. M., Butterworth, J. F. T., Di Gregorio, G., Drasner, K., Hejtmanek, M. R., et al. (2010). ASRA practice advisory on local anesthetic systemic toxicity. Regional Anesthesia and Pain Medicine, 35, 152–161.

    Article  PubMed  Google Scholar 

  25. Weinberg, G. L. (2010). Treatment of local anesthetic systemic toxicity (LAST). Regional Anesthesia and Pain Medicine, 35, 188–193.

    Article  CAS  PubMed  Google Scholar 

  26. Liu, P., Feldman, H. S., Covino, B. M., Giasi, R., & Covino, B. G. (1982). Acute cardiovascular toxicity of intravenous amide local anesthetics in anesthetized ventilated dogs. Anesthesia and Analgesia, 61, 317–322.

    CAS  PubMed  Google Scholar 

  27. Cho, H. S., Lee, J. J., Chung, I. S., Shin, B. S., Kim, J. A., & Lee, K. H. (2000). Insulin reverses bupivacaine-induced cardiac depression in dogs. Anesthesia and Analgesia, 91, 1096–1102.

    CAS  PubMed  Google Scholar 

  28. Vasques, F., Behr, A. U., Weinberg, G., Ori, C., & Di Gregorio, G. (2015). A review of local anesthetic systemic toxicity cases since publication of the american society of regional anesthesia recommendations: To whom it may concern. Regional Anesthesia and Pain Medicine, 40, 698–705.

    Article  CAS  PubMed  Google Scholar 

  29. Di Gregorio, G., Neal, J. M., Rosenquist, R. W., & Weinberg, G. L. (2010). Clinical presentation of local anesthetic systemic toxicity: A review of published cases, 1979 to 2009. Regional Anesthesia and Pain Medicine, 35, 181–187.

    Article  PubMed  Google Scholar 

  30. Kim, H. S., Cho, J. E., Hong, S. W., Kim, S. O., Shim, J. K., & Kwak, Y. L. (2010). Remifentanil protects myocardium through activation of anti-apoptotic pathways of survival in ischemia-reperfused rat heart. Physiological Research, 59, 347–356.

    CAS  PubMed  Google Scholar 

  31. Wong, G. T. C., Li, R., Jiang, L. L., & Irwin, M. G. (2010). Remifentanil post-conditioning attenuates cardiac ischemia-reperfusion injury via kappa or delta opioid receptor activation. Acta Anaesthesiologica Scandinavica, 54, 510–518.

    Article  CAS  PubMed  Google Scholar 

  32. Zhang, Y., Irwin, M. G., Wong, T. M., Chen, M., & Cao, C. M. (2005). Remifentanil preconditioning confers cardioprotection via cardiac kappa- and delta-opioid receptors. Anesthesiology, 102, 371–378.

    Article  CAS  PubMed  Google Scholar 

  33. Tanaka, K., Kersten, J. R., & Riess, M. L. (2014). Opioid-induced cardioprotection. Current Pharmaceutical Design, 20(36), 5696–5705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Glass, P. S., Gan, T. J., & Howell, S. (1999). A review of the pharmacokinetics and pharmacodynamics of remifentanil. Anesthesia and Analgesia, 89, 7–14.

    Article  Google Scholar 

  35. Reid, J. E., & Mirakhur, R. K. (2000). Bradycardia after administration of remifentanil. British Journal of Anaesthesia, 84, 422–423.

    Article  CAS  PubMed  Google Scholar 

  36. Kurdi, O., Deleuze, A., Marret, E., & Bonnet, F. (2001). Asystole during anaesthetic induction with remifentanil and sevoflurane. British Journal of Anaesthesia, 87, 943.

    CAS  PubMed  Google Scholar 

Download references

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Author information

Authors and Affiliations

  1. Department of Anesthesiology and Reanimation, School of Medicine, Bulent Ecevit University, Zonguldak, Turkey

    Özcan Pişkin & Hilal Ayoğlu

Authors
  1. Özcan Pişkin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hilal Ayoğlu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Özcan Pişkin.

Ethics declarations

Conflict of interest

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pişkin, Ö., Ayoğlu, H. Effects of Remifentanil Pretreatment on Bupivacaine Cardiotoxicity in Rats. Cardiovasc Toxicol 18, 56–62 (2018). https://doi.org/10.1007/s12012-017-9413-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12012-017-9413-3

Keywords

search

Navigation