Welcome to the next installment of the Anesthesia Patient Safety podcast hosted by Alli Bechtel. This podcast will be an exciting journey towards improved anesthesia patient safety.
Beware of medication labeling error of Cisatracurium labeled as phenylephrine. Check out the article with pictures here. https://www.apsf.org/news-updates/alert-extremely-hazardous-packaging-error-with-cisatracurium-and-phenylephrine/
Today, we are diving back into our archives to talk about local anesthetic toxicity and intralipid treatment with an article from the APSF Spring 2009 Newsletter by Pete Stiles and Richard Prielipp called, “Intralipid Treatment of Bupivacaine Toxicity.” This article is one of the most frequently visited pages on our website and you can find it here. https://www.apsf.org/article/intralipid-treatment-of-bupicavaine-toxicity/
This is also a sneak preview for a future show where we discuss “Local Anesthetic Systemic Toxicity (LAST) Revisited: A Paradigm in Evolution” from the APSF February 2020 article. This will be a special two part series on Local Anesthetic Systemic Toxicity.
Check out http://www.lipidrescue.org/ for more information and case reports of LAST.
After listening to the show, check out the newest APSF Newsletter for February 2021. You can find the Newsletter here: https://www.apsf.org/newsletter/february-2021/ We are so excited to review these articles on future show.
Ok SH, Hong JM, Lee SH, Sohn JT. Lipid Emulsion for Treating Local Anesthetic Systemic Toxicity. Int J Med Sci. 2018;15(7):713-722. Published 2018 May 14.
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© 2021, The Anesthesia Patient Safety Foundation
Hello and welcome back to the Anesthesia Patient Safety Podcast. My name is Alli Bechtel and I am your host. Thank you for joining us for another show.
First up, I want to highlight a recent news release on the APSF website. You may have already seen it, but if not, this is a very real threat to patient safety due to a medication vial packaging error. The release is called, “Alert: Extremely Hazardous Packaging Error with Cisatracurium and Phenylephrine” which was published online on January 27th, 2021. The Institute for Safe Medication Practices or ISMP reported on the incorrect labeling of Phenylephrine vials that may contain Cisatracurium from Meitheal Pharmaceuticals. I will include a link to the article in the show notes. There are pictures included in the article as well. The ISMP report states that the vials do have the vial cap marked for a paralyzing medication and it is packaged in a box labeled correctly as Cisatracurium, but the front of the vials in the box are labeled as Phenylephrine HCL. It is important that any cartons of Cisatracurium from Meitheal Pharmaceuticals is inspected carefully before any use and the FDA and manufacturer are aware of this vial labeling error and a recall was pending when this article was published on our website. When it comes to medication safety, we cannot let down our guard.
Before we dive into today’s episode, we’d like to recognize Fresenius Kabi, a major corporate supporter of APSF. Fresenius Kabi has generously provided unrestricted support as well as research and educational grants to further our vision that “no one shall be harmed by anesthesia care”. Thank you, Fresenius Kabi – we wouldn’t be able to do all that we do without you!”
Today on the show we are starting a series on Local Anesthetic toxicity. This is a very important consideration for anesthesia patient safety and APSF has several articles on the topic. First, we are going to explore the APSF Newsletter archives. For this episode and future similar shows, we will take a look at past articles that were published in the APSF Newsletter that you can find on our website. Keep in mind that things may have changed a lot since the publication of these articles, but they are of interest from our archives. In fact, this is one of the most frequently visited pages on the APSF website! I hope you have your cup of coffee or tea ready or you are out on an invigorating walk as we get ready to explore the past by looking at an area that is so important for patient safety, local anesthetic toxicity and the treatment!! There is so much to talk about related to this topic, but for our first show on the topic we are going all the way back to 2009 to look at the article by Pete Stiles and Richard Prielipp called, “Intralipid Treatment of Bupivacaine Toxicity.” Research and protocols related to local anesthetic toxicity have changed a lot since then which will give us plenty to talk about on future shows! This is also a sneak preview for a future show where we discuss “Local Anesthetic Systemic Toxicity (LAST) Revisited: A Paradigm in Evolution” from the APSF February 2020 article. While some people may consider this a spoiler alert, I just want you to be excited about an upcoming show!!
Let’s get into the 2009 article. To follow along with us, go to APSF.org and click on Newsletter heading, 4th one down is Newsletter archives. From here, scroll down to 2009 and click on Spring 2009. The 6th article in the left hand column is our featured article. Here we go!
Inadvertent intravascular injection of local anesthetic medications may lead to cardiac toxicity with the resultant hypotension, atrioventricular conduction delay, idioventricular rhythms, and cardiovascular collapse. Bupivacaine deserves special recognition since though all local anesthetic medications can decrease the myocardial refractory period, bupivacaine readily blocks cardiac sodium channels and is the most likely to cause cardiac arrhythmias and cardiovascular collapse. Keep in mind that levobupivacaine and ropivacaine were created with the hopes of minimizing the adverse cardiac effects, but these medications are still able to alter cardiac rhythm and function. Back in 2009, we were seeing local anesthetic systemic toxicity or LAST in 20 out of 10,000 peripheral nerve blocks and 4 out of 10,000 epidural procedures. Since then, we have increased the types and frequency with which we use peripheral nerve blocks and the authors recognized this trend and gave all anesthesia professionals a call to action to know the signs of local anesthetic cardiotoxicity and stay up to date with treatment recommendations. This is also a frequently tested topic for all anesthesia trainees. More recent data from large registries and administrative databases reveal a rate of LAST of about 1 in every 1000 peripheral nerve blocks, but keep in mind that this is very likely an underestimation due to under-reporting, failed diagnosis and other difficulties with reporting LAST events.
Returning to the 2009 article, the authors discuss treatment with intralipid and start with a literature review. Earlier research revealed that lipid infusion in rats prior to IV administration of bupivacaine led to an increase in the bupivacaine dose that induced asystole while giving administration of intralipid after iv bupivacaine led to better hemodynamics and faster myocardial metabolism. Around this time the phrase “lipid rescue” emerged and there was a push for lipid emulsions to be available anywhere regional or epidural anesthesia procedures were performed such as in preop holding area and up on the OB floor. At the same time, anesthesia professionals continued to advocate for safe performance of the blocks with appropriate medication dosing to minimize the risk of LAST rather than relying on lipid rescue.
Intralipid to the rescue…[superhero music]…
The authors describe a case report of a 58-year-old man who underwent interscalene nerve block and subsequently developed a tonic-clonic seizure followed by cardiac arrest approximately 30 seconds after the block. ACLS was started but the patient remained without a perfusing rhythm. He was given 100mls of 20% intrepid with continued CPR. During the next defibrillation, the patient returned to a sinus rhythm and his hemodynamics improved with appropriate inotropic and vasopressor support. Intralipid infusion at 0.5ml/kg/min was continued for the next 2 hours and the patient’s clinical status continued to improve with return of consciousness and intact neurological function.
For this case, it really does seem like intralipid deserves the title of lipid rescue and it is a good thing that it was available following the development of LAST for the patient in the case report that we just talked about. But this case report does leave us with some questions including: “What is the mechanism of action of lipid rescue?” and “Is the beneficial effect of Intralipid promoted or hindered by concurrent drug therapy administered via ACLS protocol?” At the time of this article, the reports suggested that early intralipid treatment was beneficial and that intralipid could be used for last due to other local anesthetics and not just bupivacaine. In addition, the proposed mechanism for lipid rescue was by helping to increase the clearance of the highly lipid-soluble local anesthetic medications from cardiac tissue by absorption into the lipid emulsion being administered into the plasma and thus acting as a “lipid sink.” The lipid sink theory is still one of the proposed mechanisms today. It was also thought that the intralipids opposed the inhibition of myocardial fatty acid oxidation caused by local anesthetics by providing a fatty acid supply leading to return of myocardial energy production and improved cardiac function.
Additional research has suggested additional mechanisms may be at work including redistribution of the local anesthetics from the heart to the liver, intrinsic inotropic effects of intralipid, cell signaling pathways leading to decreased ischemia/reperfusion injury, increased systemic vascular resistance due to deceased nitric oxide release, and reversal of the cardiac sodium channel blockade caused by the local anesthetics. The authors remind us that we still need to exercise caution every time we use local anesthetics and prevention of LAST is still a top priority. Even though we may be able to rescue a patient who suffers cardiac arrest from LAST, there is still a big risk for decreased neurological function following the arrest. For continued anesthesia safety, you will want to consider using intralipid, but it is important to continue to use guidelines for the safe use of local anesthetics including ECG, blood pressure, and pulse oximeter monitoring, appropriate dosing of local anesthetics with good techniques for these procedures, immediately available ventilation support, high quality CPR and chest compressions with additional life support techniques when needed.
Considerations for the use of intralipid for cases of bupivacaine and other local anesthetic-related systemic toxicity include the following: there is a role for this medication for resuscitation and ACLS following LAST, but intralipid may affect ACLS drug action and the dosing strategies and recommendations in 2009 were not uniform. Survey data academic anesthesiology departments from 2006 revealed that 26% would consider using lipid rescue to treat LAST. Intralipid was stored most often in the OR pharmacy followed by the hospital pharmacy with 22% storing this medication in a code box and only 4% having this medication stored in a drug-dispensing device in the OR. Protocols for LAST treatment began to include the use of intralipid in the algorithms as well. There was a call for intralipid to be available at all locations where local anesthetics were being administered to patients as well as a call for additional research.
For more information about lipid rescue and to read case reports, you can head over to www.lipidrescue.org. This website was created by Guy Weinburg. Weinburg is also one of the authors of the February 2020 ASPF article on LAST revisited that we will be discussing in an upcoming show. I will include a link to the website in the show notes.
The authors left us with some questions in 2006:
- Should the lipid dose be titrated, by patient weight, local anesthetic dose, or the symptoms/ signs/severity of toxicity?
- What is the best rate and total dose of the infusion that follows bolus dosing? Is there a safe upper limit of lipid dosing?
- How long should the patient receive the lipid infusion?
- What is the risk of reoccurrence of toxicity once the lipid infusion is stopped?
- Should lipid emulsion be used for patients exhibiting signs of CNS toxicity, or should intralipid only be used for cardiac toxicity?
- What are the possible complications or adverse effects of lipid infusion?
- Should lipid be used alone or in combination with epinephrine, and other components of standard resuscitative measures?
- What is better, 20% or 30% lipid? What formulation is best?
- Intralipid has been used predominantly so far, but is there a better choice?
- Do the other available lipid emulsions work as well?
We hope to be able to answer some of these questions when we return to our discussion of LAST and treatment on a future show.
The authors also leave us with a treatment protocol for LAST and the resultant cardiovascular collapse after standard resuscitation that includes the following:
- Administration of 20% intralipid 1.5 mL/kg as an initial bolus; which may be repeated 1- 2 times for persistent asystole.
- Followed by initiation of an infusion of 20% intralipid at 0.25 mL/kg/min for 30-60 minutes with increased infusion rates up to 0.50 mL/kg/min for persistent and refractory hypotension.
LAST falls under several of the APSF Patient Safety Priorities include the first priority: preventing, detecting, and mitigating clinical deterioration in the perioperative period since appropriate patient monitoring during peripheral nerve block and epidural placement is crucial. The second priority since these procedures are often performed in non-operating room locations and the 4th priority involving medication safety. As we wrap up for today and return to the present, it is important to remember that local anesthetic toxicity is remains a threat to anesthesia patient safety and we must stay vigilant.
If you have any questions or comments from today’s show, please email us at [email protected]. Visit APSF.org for detailed information and check out the show notes for links to all the topics we discussed today. Whether you are listening to the podcast on our website or have subscribed on iTunes or Spotify or where ever you get your podcasts, thanks for listening!! Stay tuned for more great shows especially since the February 2021 APSF newsletter is out! That’s right…the newest APSF newsletter is now available on line and you do not want to miss it. I will include a link in the show notes and I am so excited to talk about some of these articles and introduce some of these authors on future shows!
Until next time, stay vigilant so that no one shall be harmed by anesthesia care.
© 2021, The Anesthesia Patient Safety Foundation