Lipid Emulsion Treatment for Local Anesthetic Systemic Toxicity

Local anesthetics are used by dentists extensively and when used erroneously, such as intravenously or above the maximum dose, life-threatening local anesthetic systemic toxicity (LAST) can result. The signs and symptoms of LAST can appear immediately after injection if injected directly into a blood vessel or delayed if the anesthetic is absorbed from the tissue at the site of injection.¹ The life-threatening complications are due to effects on the central nervous system (CNS) and cardiovascular system (CVS) through depression of electrical conduction. CNS depression with loss of consciousness and seizures, are the most common characteristics of LAST.¹ At high concentrations, circulatory collapse and asystole can occur and cardiac resuscitation is required.¹ Lipid emulsion has been recognised as a life-saving treatment for LAST and has been applied to medical anesthesia guidelines since 2010.^1,2 However, despite the widespread use of local anesthetics by dental practitioners, over half of surveyed dentists are unaware of lipid emulsion treatment for LAST and fewer then 2% know how to use it.³

Lipid emulsion is offered commercially as Intralipid 10% or 20% which as been available since 1962.¹ It consists of egg phospholipids, soybean oil, and glycerin.² Lipid emulsion is used predominately in the medical field for patients in the intensive care unit who suffer from malnutrition.¹ Patients receive slow lipid infusion over a 12- to 24-hour period as a caloric and fatty acid source.^1,2

Dr. Guy Weinberg first suggested lipid emulsion can be used for treatment of local anesthesia toxicity when he observed that intravenous lipid infusion increases the dosage of bupivacaine required to cause asystole in both rats and dogs.^4,5 Furthermore, he demonstrated that lipid infusion during resuscitation from bupivacaine-induced cardiac arrest in dogs improved survival.⁴ His hypothesis was that lipid emulsion forms a “lipid sink”, a lipid phase that extracts the lipid-soluble anesthetic molecules from the body’s plasma.⁵ Dr. Weinberg suggested that in humans where resuscitation due to LAST is required, a 1 mL/kg bolus of 20% lipid emulsion over 1 minute be used and repeated every 3-5 minus to a maximum of 3 mL/kg.⁶ Following resumption of normal sinus rhythm, Dr. Weinberg suggested an infusion of 20% lipid emulsion, at a rate of 0.25 mL/kg/min be used until the patient has stable hemodynamics.⁶ Though, at the time of these suggestions, Dr. Weinberg’s dose-response research was ongoing and his suggested dosages were provided in a “to the editor” response letter.⁶

The first use of lipid emulsion to resuscitate a patient following cardiac arrest occurred in 2006 by Dr. Rosenblatt and team.⁷ A 58-year-old male received a spinal block with bupivacaine for
arthroscopic repair of a torn rotator cuff. Approximately 30 seconds following injection, the patient developed a tonic-clonic seizure that eventual lead to asystole (no pulse). Advanced cardiovascular life support was provided and after 20 minutes of resuscitation with periods of pulse resumption that relapsed to asystole, 100 mL of 20% Intralipid was initiated intravenously. Within 15 seconds, regular sinus rhythm resumed, and blood pressure and pulse were detectable. Infusion of lipid emulsion was continued for 2.5 hours at which time the patient was awake and responsive. The dosage of 20% intralipid used was a bolus of 1.2 mL/kg followed by infusion of 0.5 mL/kg/min. This dosage was more then suggested by Dr. Weinberg. However, the patient was observed for two weeks following the administration of intralipid with no deleterious effects seen.

Following Dr. Rosenblatt’s successful use of lipid emulsion for LAST resuscitation, more than 19 case reports have been published that have successfully utilized lipid emulsion for treatment of LAST.² The American Society of Regional Anesthesia and Pain Medicine (ASRA) first published its practice advisory guidelines for lipid emulsion treatment of LAST in 2010. It has since updated their guidelines regularly in response to user feedback, simulation studies and advances in medical knowledge.⁸ Their 2020 guidelines state that when LAST is suspected, the first step is call for help and consider administering intravenous lipid emulsion intravenously early.⁸ If the patient is over 70 kg, a 100 mL bolus of 20% lipid emulsion over two to three minutes then infuse 250 mL over 15-20 minutes. If the patient is less then 70 kg, bolus 1.5 mL/kg over 2-3 minutes and infuse 0.25 mL/kg/min. If patient remains unstable, repeat bolus and double infusion. For arrhythmias and cardiac arrest, advanced cardiovascular life support guidelines should be followed. The ASRA local anesthetic systemic toxicity checklist can be accessed at www.asra.com.⁸

To prevent LAST, it is important not to exceed the safe dose of the local anesthetic used. The maximum dose of local anesthetic depends on patient-specific factors such as extremes of age, weight, pregnancy, and co-morbidities such as renal disease or liver disease.^1,3 Furthermore, it is recommended to always aspirate before each injection to rule out intravascular needle placement before administering local anaesthetics.⁹ Likewise, it is recommended that a pause of one circulation time (15-45 seconds) be used between cartridge injections to allow for observation of LAST signs and symptoms in the event of intravenous injection, as needle aspiration has a false negative rate of 2%.² As LAST is a life-threatening situation, the signs and symptoms must be recognized and treated quickly. Lipid emulsion treatment is potentially lifesaving and knowledge of its use by dental physicians is important for safe patient care.

Oral Health welcomes this original article.

References

1. Rhee, S.-H., Park, S.-H., Ryoo, S.-H. & Karm, M.-H. Lipid emulsion therapy of local anesthetic systemic toxicity due to dental anesthesia. J Dent Anesth Pain Med 19, 181-189, doi:10.17245/jdapm.2019.19.4.181 (2019).
2. Ciechanowicz, S. J. & Patil, V. K. Intravenous lipid emulsion – rescued at LAST. British Dental Journal 212, 237-241, doi:10.1038/sj.bdj.2012.187 (2012).
3. Oksuz, G. et al. Dentists knowledge of lipid treatment of local anaesthetic systemic toxicity. Niger J Clin Pract 21, 327-331, doi:10.4103/njcp.njcp_12_17 (2018).
4. Weinberg, G., Ripper, R., Feinstein, D. L. & Hoffman, W. Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity. Reg Anesth Pain Med 28, 198-202, doi:10.1053/rapm.2003.50041 (2003).
5. Weinberg, G. L., VadeBoncouer, T., Ramaraju, G. A., Garcia-Amaro, M. F. & Cwik, M. J. Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats. Anesthesiology 88, 1071-1075, doi:10.1097/00000542-199804000-00028 (1998).
6. Weinberg, G. Reply to Drs. Goor, Groban, and Butterworth—Lipid Rescue: Caveats and Recommendations for the “Silver Bullet”. Regional Anesthesia & Pain Medicine 29, 74-75, doi:10.1016/j.rapm.2003.11.009 (2004).
7. Rosenblatt, Meg A., Abel, M., Fischer, Gregory W., Itzkovich, Chad J. & Eisenkraft, James B. Successful Use of a 20% Lipid Emulsion to Resuscitate a Patient after a Presumed Bupivacaine-related Cardiac Arrest. Anesthesiology 105, 217-218, doi:10.1097/00000542-200607000-00033 (2006).
8. Neal, J. M., Neal, E. J. & Weinberg, G. L. American Society of Regional Anesthesia and Pain Medicine Local Anesthetic Systemic Toxicity checklist: 2020 version. Regional Anesthesia & Pain Medicine, rapm-2020-101986, doi:10.1136/rapm-2020-101986 (2020).
9. Raghavan, M. D. Aspirate before injecting the local anaesthetic–Is it necessary ? BJA: British Journal of Anaesthesia 101, doi:10.1093/bja/el_2631 (2008).

About the Author

Dr. Cameron Goertzen is a current second year resident in the Dental Anesthesia program at the University of Toronto and is a U of T DDS graduate. He has a diverse background in research and has published articles in the fields of dental anesthesiology, breast cancer and oral cancer. Cameron is from the Niagara Region and together with his wife, Dr. Erin Goertzen, a pediatric dental resident at U of T, he hopes to practice in the Region following the completion of their respective studies.