Now wouldn't it be great if we could extend the duration of action of our nerve block and offer extended comfort to our patients? In this Pain Update we look at some ways in which this can happen. Firstly we look at liposomal bupivacaine and then we look at the addition of dexmedetomidine to our regular local anaesthetic solutions.
Liposomal bupivacaine is a formulation designed to extend the duration of analgesic effects compared to traditional bupivacaine. If you like a video, you can see how liposomal bupivacaine works here.
1. Liposomal Encapsulation: Bupivacaine is encapsulated in liposomes, which are small spherical vesicles made from lipid bilayers. These liposomes act as a delivery system that controls the release of the drug over an extended period.
2. Sustained Release: Once administered, the liposomes gradually release bupivacaine into the surrounding tissues. This slow release mechanism ensures a prolonged effect compared to the immediate release seen with standard bupivacaine formulations.
3. Mechanism of Action: Bupivacaine itself works by blocking sodium channels on nerve cells, which inhibits the propagation of nerve impulses responsible for pain sensation. By maintaining a steady concentration of bupivacaine at the site of administration, liposomal bupivacaine provides continuous pain relief.
4. Prolonged Analgesia: The encapsulation in liposomes allows for a more sustained therapeutic effect, potentially providing pain relief for up to 72 hours or longer, depending on the formulation and site of administration.
This extended release profile of liposomal bupivacaine makes it particularly useful in postoperative pain management, reducing the need for additional analgesics and improving patient comfort.
Exparel, a brand of liposomal bupivacaine used in human medicine, is indicated for:
1. Postsurgical Analgesia: Exparel is used to provide extended postoperative pain relief in patients undergoing various surgical procedures. Its sustained-release formulation helps manage pain for up to 72 hours, reducing the need for opioids and improving patient recovery and comfort.
2. Interscalene Brachial Plexus Block: Exparel is indicated for single-dose administration in adults to produce postsurgical local and regional anesthesia following shoulder surgeries, such as rotator cuff repair.
These indications allow for effective pain management in postoperative settings, helping to reduce opioid consumption and improve patient outcomes by providing prolonged analgesia.
If you look into the literature the story around this particular product, you uncover a healthy degree of scepticism.
“…liposomal bupivacaine was found to be superior to comparators in 46% of…conflicted [pharma-sponsored] trials but was found to be superior in only 11% of the nonconflicted trials.”
This is a quote from this review published in the journal Anesthesiology in 2021. It's worth a read! The article ends with;
To summarize, both the review by Ilfeld et al. and the meta-analysis by Hussain et al. concluded that liposomal bupivacaine did not show clinical superiority over existing, active comparators, nonliposomal bupivacaine or ropivacaine.
Prior to 2021 and this publication, I tried to obtain some Exparel in the UK, but wasn't successful - and I think we can see the advantages that it could offer to our patients. IN the USA, there is a veterinary licensed product called Nocita - but we don't have that in Europe.
Nocita, a brand of liposomal bupivacaine, is primarily indicated for use in veterinary medicine. Its specific indications include:
1. Postoperative Pain Management in Dogs: Nocita is used to provide long-lasting local analgesia following cranial cruciate ligament (CCL) surgery. The sustained-release formulation helps manage postoperative pain for up to 72 hours, improving recovery and reducing the need for additional pain medications.
2. Postoperative Pain Management in Cats: Nocita is also indicated for use in cats to provide local analgesia for up to 72 hours following certain surgical procedures. It helps manage pain and enhances postoperative recovery. (Some of these procedures are declaw procedures, which in Europe we deem unethical and do not perform - you can imagine you would want long acting anaesthesia after such a procedure. Poor cats.)
This is a nice article which reviews Nocita in dogs and cats.
These are specific indications which the product is licensed for. There is certainly an advantage to long acting local anaesthesia of sensory nerves, however it could be a disadvantage say for example in a femoral and sciatic nerve block where would would see motor effects for up to 72hrs.
A sensory block where you can see a benefit to prolonged anaesthesia is the transversus abdominis plane (TAP) block. The TAP offers anaesthesia to the abdominal wall and is a block that I commonly perform in exploratory celiotomy cases. In this study, the authors compared the use of liposome encapsulated bupivacaine (BLS) to a combination of dexmedetomidine and bupivacaine. The results from the study are quoted as;
A TAP block appeared to provide adequate postoperative analgesia for abdominal surgery in the dogs of the present study undergoing elective ovariohysterectomy. The BLS TAP block did not appear to provide any extra benefit beyond what BUP-DEX TAP block added under these specific conditions.
On a practical note, the use of dexmedetomidine is also much cheaper than the BLS.
If we look at the use of dexmedetomidine as an adjunct to local anaesthesia, we see the following questions:
Can dexmedetomidine extend block duration?
Yes, dexmedetomidine can extend the duration of a bupivacaine block. Dexmedetomidine is an alpha-2 adrenergic agonist known for its sedative, analgesic, and anxiolytic properties. When used as an adjuvant to local anaesthetics like bupivacaine, it can enhance and prolong the analgesic effects. This is an example of a meta-analysis looking at the use of dexmedetomidine alongside ropivacaine.
How does it work alongside local anaesthetics?
Prolonged Analgesia: Dexmedetomidine, when added to bupivacaine, can extend the duration of sensory and motor blocks. This is achieved through synergistic effects, where dexmedetomidine enhances the local anaesthetic action of bupivacaine by blocking nerve conduction more effectively and for a longer period.
Mechanism of Action: Dexmedetomidine works by binding to alpha-2 adrenergic receptors, which leads to a decrease in norepinephrine release and subsequent modulation of pain pathways. This action can complement the sodium channel blocking effect of bupivacaine, resulting in enhanced and prolonged analgesia.
Clinical Benefits: The combination of dexmedetomidine with bupivacaine can result in longer-lasting pain relief, potentially reducing the need for additional analgesics postoperatively. It can also improve patient comfort and satisfaction by providing extended periods of pain relief. It would have helped in the above TAP block study if the authors had a bupivacaine along group - that way we could really dissect out the differences.
Overall, the addition of dexmedetomidine to bupivacaine is a valuable strategy in various regional anesthesia techniques to achieve longer-lasting and more effective pain control.
In light of this review, we can see the benefits of prolonged anaesthesia giving us extended analgesia and I am sure you are considering which patients this could be useful in. At the moment we don't have a veterinary BLS product in Europe - but do we need it if we can add dexmedetomidine?
References
Campoy L, Martin-Flores M, Boesch JM, Moyal MN, Gleed RD, Radhakrishman S, Pavlinac RM, Sieger JL, Colon CS, Magidenko SR. Transverse abdominis plane injection of bupivacaine with dexmedetomidine or a bupivacaine liposomal suspension yielded lower pain scores and requirement for rescue analgesia in a controlled, randomized trial in dogs undergoing elective ovariohysterectomy. Am J Vet Res. 2022 Jul 22;83(9):ajvr.22.03.0037. doi: 10.2460/ajvr.22.03.0037. PMID: 35895764.
Li F, Guo L, Huang Z, Lin F, Pan L. Effects of dexmedetomidine as an adjuvant to ropivacaine or ropivacaine alone on duration of postoperative analgesia: A systematic review and meta-analysis of randomized controlled trials. PLoS One. 2023 Oct 11;18(10):e0287296. doi: 10.1371/journal.pone.0287296. PMID: 37819905; PMCID: PMC10566714.
McCann ME. Liposomal Bupivacaine: Effective, Cost-effective, or (Just) Costly?. Anesthesiology 2021; 134:139–142 doi: https://doi.org/10.1097/ALN.0000000000003658
This post was written by Matt Gurney.
Matt & Carl established Zero Pain Philosophy to provide educational resources & telemedicine to veterinary professionals globally, enabling optimal management of pain.
Matt Gurney is an RCVS & European Specialist in Veterinary Anaesthesia & Analgesia and works at Anderson Moores Veterinary Specialists. Matt is Past President of the European College of Veterinary Anaesthesia & Analgesia and works at Eastcott Referrals in the UK.
Carl Bradbrook is an RCVS & European Specialist in Veterinary Anaesthesia & Analgesia and is Past President of the Association of Veterinary Anaesthetists. Carl works at Anderson Moores Veterinary Specialists in the UK.
The intended audience for this pain update is veterinary professionals. This pain update is based on clinical experience and independent opinion.