Lipid emulsion mitigates local anesthesia‑induced central nervous system toxicity in rats

Wu,Gangming; Sun,Bin; Liu,Li; Zhou,Jun; Mo,Liqun; Ren,Changhe; Ou,Cehua

doi:10.3892/etm.2015.2594

September-2015 Volume 10 Issue 3

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

September-2015 Volume 10 Issue 3

Full Size Image

Article

Lipid emulsion mitigates local anesthesia‑induced central nervous system toxicity in rats

Authors:
- Gangming Wu
- Bin Sun
- Li Liu
- Jun Zhou
- Liqun Mo
- Changhe Ren
- Cehua Ou
View Affiliations / Copyright

Affiliations: Department of Anesthesiology and Pain, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, P.R. China
Pages: 1133-1138
|
Published online on: June 24, 2015

https://doi.org/10.3892/etm.2015.2594
Expand metrics +

Abstract

The aim of the present study was to investigate the effect of intravenously administered lipid emulsion on local anesthetic (LA)‑induced central nervous system (CNS) toxicity. A total of 100 male Sprague Dawley rats were allocated at random into the following groups: Sham (A), lidocaine (B), levobupivacaine (C) and ropivacaine (D). Groups B‑D were each subdivided into three subgroups: Toxic, post‑conditioning and pre‑conditioning. Intracerebroventricular injections of 0.9% normal saline (sham group) or LA were administered via microsyringe; in addition, a 20% lipid emulsion was injected into tail vein prior to the LA injection (pre‑conditioning subgroups) or following rat respiratory arrest (post‑conditioning subgroups). The heart rate, blood pressure, neurological behavior scores, neuronal density and time from LA injection to respiratory arrest, apnea and start of arrhythmia were measured. Rats in the toxic groups died due to respiratory arrest following the injection of LA into the lateral ventricle. Rats in the post‑conditioning subgroups were resuscitated from the LA‑induced respiratory arrest, while the pre‑conditioning subgroup rats exhibited no respiratory arrest. No significant differences in heart rate were observed between the toxic and post‑conditioning subgroups in the levobupivacaine and ropivacaine groups (P>0.05); however, a significant difference was observed between these treatment groups and the rats treated with lidocaine (P<0.01). A significant difference was also observed in the time from the LA injection to the onset of arrhythmia among the rats in groups B, C and D (P<0.01). No significant differences in the neurological behavior scores and neuronal density were observed in the hippocampal CA1 zone among group C and D rats in the post- and pre-conditioning subgroups at various time-points following treatment. Beyond that, the same phenomena regarding neurological behavior scores was observed in post- and pre-conditioning subgroups of group B at 12 and 24 h treatment, contrasting with the statistically significant difference between post- and pre-conditioning subgroups at 6 h treatment (P<0.01). The results of the present study therefore indicate that pre‑ and post‑conditioning with lipid emulsion effectively mitigates LA‑induced CNS toxicity in rats.

View Figures

View References

1	Wolfe JW and Butterworth JF: Local anesthetic systemic toxicity: Update on mechanisms and treatment. Curr Opin Anaesthesiol. 24:561–566. 2011. View Article : Google Scholar : PubMed/NCBI
2	Zink W and Graf BM: Toxicology of local anesthetics. Clinical, therapeutic and pathological mechanisms. Anaesthesist. 52:1102–1123. 2003.(In German). View Article : Google Scholar : PubMed/NCBI
3	Weinberg GL, VadeBoncouer T, Ramaraju GA, Garcia-Amaro MF and Cwik MJ: Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats. Anesthesiology. 88:1071–1075. 1998. View Article : Google Scholar : PubMed/NCBI
4	Rosenblatt MA, Abel M, Fischer GW, Itzkovich CJ and Eisenkraft JB: Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest. Anesthesiology. 105:217–218. 2006. View Article : Google Scholar : PubMed/NCBI
5	Litz RJ, Popp M, Stehr SN and Koch T: Successful resuscitation of a patient with ropivacaine-induced asystole after axillary plexus block using lipid infusion. Anaesthesia. 61:800–801. 2006. View Article : Google Scholar : PubMed/NCBI
6	Oda Y and Ikeda Y: Effect of lipid emulsion on the central nervous system and cardiac toxicity of bupivacaine and levobupivacaine in awake rats. J Anesth. 27:500–504. 2013. View Article : Google Scholar : PubMed/NCBI
7	Sakai T, Manabe W, Kamitani T, Takeyama E and Nakano S: Ropivacaine-induced late-onset systemic toxicity after transversus abdominis plane block under general anesthesia: Successful reversal with 20% lipid emulsion. Masui. 59:1502–1505. 2010.(In Japanese). PubMed/NCBI
8	Dix SK, Rosner GF, Nayar M, et al: Intractable cardiac arrest due to lidocaine toxicity successfully resuscitated with lipid emulsion. Crit Care Med. 39:872–874. 2011. View Article : Google Scholar : PubMed/NCBI
9	Weinberg GL: Treatment of local anesthetic systemic toxicity (LAST). Reg Anesth Pain Med. 35:188–193. 2010. View Article : Google Scholar : PubMed/NCBI
10	Foxall G, McCahon R, Lamb J, Hardman JG and Bedforth NM: Levobupivacaine-induced seizures and cardiovascular collapse treated with Intralipid. Anaesthesia. 62:516–518. 2007. View Article : Google Scholar : PubMed/NCBI
11	Lange DB, Schwartz D, DaRoza G and Gair R: Use of intravenous lipid emulsion to reverse central nervous system toxicity of an iatrogenic local anesthetic overdose in a patient on peritoneal dialysis. Ann Pharmacother. 46:e372012. View Article : Google Scholar : PubMed/NCBI
12	Weinberg G, Lin B, Zheng S, et al: Partitioning effect in lipid resuscitation: Further evidence for the lipid sink. Crit Care Med. 38:2268–2269. 2010. View Article : Google Scholar : PubMed/NCBI
13	Dong WK, Bledsoe SW, Eng DY, et al: Profound arterial hypotension in dogs: Brain electrical activity and organ integrity. Anesthesiology. 58:61–71. 1983. View Article : Google Scholar : PubMed/NCBI
14	Dong WK, Bledsoe SW, Chadwick HS, Shaw CM and Hornbein TF: Electrical correlates of brain injury resulting from severe hypotension and hemodilution in monkeys. Anesthesiology. 65:617–625. 1986. View Article : Google Scholar : PubMed/NCBI
15	Weinberg G, Ripper R, Feinstein DL and Hoffman W: Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity. Reg Anesth Pain Med. 28:198–202. 2003. View Article : Google Scholar : PubMed/NCBI
16	Mulroy MF: Systemic toxicity and cardiotoxicity from local anesthetics: Incidence and preventive measures. Reg Anesth Pain Med. 27:556–561. 2002. View Article : Google Scholar : PubMed/NCBI
17	Aumeier C, Kasdor B, Gruber M, et al: Lipid emulsion pretreatment has different effects on mepivacaine and bupivacaine cardiac toxicity in an isolated rat heart model. Br J Anaesth. 112:735–741. 2014. View Article : Google Scholar : PubMed/NCBI
18	Litz RJ, Roessel T, Heller AR and Stehr SN: Reversal of central nervous system and cardiac toxicity after local anesthetic intoxication by lipid emulsion injection. Anesth Analg. 106:1575–1577, table of contents. 2008. View Article : Google Scholar : PubMed/NCBI
19	Ok SH, Sohn JT, Baik JS, et al: Lipid emulsion reverses Levobupivacaine-induced responses in isolated rat aortic vessels. Anesthesiology. 114:293–301. 2011. View Article : Google Scholar : PubMed/NCBI
20	Mather LE, Copeland SE and Ladd LA: Acute toxicity of local anesthetics: Underlying pharmacokinetic and pharmacodynamic concepts. Reg Anesth Pain Med. 30:553–566. 2005. View Article : Google Scholar : PubMed/NCBI
21	Groban L: Central nervous system and cardiac effects from long-acting amide local anesthetic toxicity in the intact animal model. Reg Anesth Pain Med. 28:3–11. 2003. View Article : Google Scholar : PubMed/NCBI
22	Chang DHT, Ladd LA, Copeland S, et al: Direct cardiac effects of intracoronary bupivacaine/levobupivacaine and ropivacaine in the sheep. Br J Pharmacology. 132:649–658. 2001. View Article : Google Scholar
23	Casati A, Chelly JE, Cerchierini E, et al: Clinical properties of levobupivacaine or racemic bupivacaine for sciatic nerve block. J Clin Anesth. 14:111–114. 2002. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Lipid emulsion mitigates local anesthesia‑induced central nervous system toxicity in rats

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Related Articles