Effective analgesia, in particular epidural anesthesia, is a much discussed and essential part of optimizing patient care. Epidural anesthesia is both safe and inexpensive with the purpose of providing intra- and postoperative pain control1. Epidurals often involve a multidrug regimen with adjuvants added to a long-acting local anesthetic such as ropivacaine. Using adjuvants is advantageous as the anesthetic and analgesic doses can be reduced while often achieving analgesia and anesthesia quicker. This article will examine adjuvants to ropivacaine and provide a comparison of the different options.
Opioids have commonly been used as adjuvants, but their adverse effects of respiratory depression, and nausea and vomiting, especially in older patients, have limited their usage2. Steroids, such as dexamethasone, as well as anti-inflammatory drugs, like parecoxib and lornoxicam, have been used as adjuvants with varying success2. Epinephrine is another adjuvant, which has long been used alongside various anesthetic agents. However, continuous infusions of epinephrine have been associated with neurotoxicity, limiting the ability to use it for epidural infusions3. Midazolam, which acts on benzodiazepine receptors, and fentanyl, an NMDA receptor antagonist, have both also been explored as anesthetic adjuvants. However, both midazolam and fentanyl are not recommended for peripheral blocks, and there is concern surrounding neurotoxicity in both agents4, 5. By far the most common adjuvants for anesthesia are the alpha agonists clonidine and dexmedetomidine. A comparison of ropivacaine adjuvants has shown clonidine and dexmedetomidine to have both sedating and analgesic effects, but with less harmful adverse effects than other options6.
When comparing alpha-2 adrenergic agonists, studies have shown that both clonidine and dexmedetomidine result in more rapid onset of anesthesia with longer duration when added to an anesthetic7. One study found that using dexmedetomidine resulted in faster onset and longer duration of pain control than clonidine1. Dexmedetomidine also demonstrated acceptable hemodynamic stability and sedation. The side effects of both include bradycardia, hypotension, nausea and itching. Importantly, respiratory depression has not been noted in patients given clonidine or dexmedetomidine adjuvants, giving them an edge over other agents such as opioids3. These adjuvants have been shown to be useful not only in epidurals but nerve blocks as well, including peripheral, axillary, and sciatic nerve blocks.
Current research in the realm of anesthetic adjuvants is directed at finding a drug that both prolongs anesthesia duration but with safer adverse effect profiles. Novel approaches include the usage of charged molecules such as tonicaine and n-butyl tetracaine, neuromuscular blocking agents, and even adenosine. However, there has been concern regarding neuromuscular blocking agents and the association with anesthetic toxicity as well as prolonged motor blockade. Meanwhile, adenosine did not have neurotoxicity concerns but was found to have no additional benefit for peripheral nerve blocks2. Further studies are warranted to search for and provide a comparison of potential other adjuvants to ropivacaine and other anesthetics, with the goal of improved safety profiles and enhanced analgesic effects, that may be used in diverse settings including the operating room, the ICU, and labor and delivery wards.
References
1 Soni P. Comparative study for better adjuvant with ropivacaine in epidural anesthesia. Anesth Essays Res 2016; 10 (2): 218-222.
2 Swain A, Nag DS, Sahu S et al. Adjuvants to local anesthetics: Current understanding and future trends. World J Clin Cases 2017; 5 (8): 307-323.
3 Neal JM. Effects of epinephrine in local anesthetics on the central and peripheral nervous systems: Neurotoxicity and neural blood flow. Reg Anesth Pain Med 2003; 28 (2): 124-134.
4 Lee IO, Kim WK, Kong MH et al. No enhancement of sensory and motor blockade by ketamine added to ropivacaine interscalene brachial plexus blockade. Acta Anaesthesiol Scand 2002; 46 (7): 821-826.
5 Kirksey MA, Haskins SC, Cheng J et al. Local Anesthetic Peripheral Nerve Block Adjuvants for Prolongation of Analgesia: A Systematic Qualitative Review. PLoS One 2015; 10 (9): e0137312.
6 Kamibayashi T, Maze M. Clinical uses of alpha2 -adrenergic agonists. Anesthesiology 2000; 93 (5): 1345-1349.
7 El-Hennawy AM, Abd-Elwahab AM, Abd-Elmaksoud AM et al. Addition of clonidine or dexmedetomidine to bupivacaine prolongs caudal analgesia in children. Br J Anaesth 2009; 103 (2): 268-274.