Adjuvants are medications that are added to local anesthetics to enhance the efficacy of nerve blocks. These agents, when combined with local anesthetics, can improve the onset, intensity, and duration of nerve blocks, providing better pain control during and after surgeries. Adjuvants can also help reduce the required dose of anesthetics, thus minimizing potential side effects. The comparison and selection of adjuvants for nerve blocks depends on the duration and level of analgesia needed, drug availability, and anesthesiologist preference.

Opioids, like fentanyl and morphine, are commonly used as adjuvants in nerve blocks. They primarily work by binding to opioid receptors, providing significant analgesic effects. The addition of opioids can prolong the duration of analgesia, particularly in neuraxial blocks. Fentanyl has a rapid onset, while morphine provides prolonged analgesia. However, opioids come with a risk of side effects such as respiratory depression, pruritus, nausea, and vomiting, especially when used in higher doses or in neuraxial blocks 1,2. Opioids remain important tools in clinical practice, but for many situations, a comparison with other adjuvants for nerve blocks reveals safer options with similar efficacy.

Alpha-2 adrenergic agonists such as clonidine and dexmedetomidine have gained popularity as adjuvants due to their sedative and analgesic properties. These agents can significantly prolong the duration of nerve blocks, reduce opioid consumption, and provide sedation. Dexmedetomidine is more selective for alpha-2 receptors than clonidine, offering a more potent analgesic effect with fewer side effects. Both drugs can cause hypotension and bradycardia, especially when administered in high doses. Careful monitoring is required during administration 3–5.

Dexamethasone is a potent anti-inflammatory agent used as an adjuvant in nerve blocks. Dexamethasone, when added to local anesthetics, can prolong the duration of analgesia by reducing inflammatory responses and nerve excitability. It has been shown to extend analgesia duration in many cases, without significant side effects at typical doses. However, there are concerns about potential neurotoxicity with high doses of steroids 2,6.

Epinephrine is often used as an adjuvant to reduce the systemic absorption of local anesthetics, thereby prolonging their duration of action. Epinephrine limits the spread of the anesthetic through local vasoconstriction. It also helps identify accidental intravascular injections. However, epinephrine can cause tachycardia, hypertension, and ischemia in tissues with poor blood supply, particularly in end-artery areas such as fingers or toes 2,4,7.

Magnesium, a non-opioid adjuvant, has been shown to modulate pain by blocking N-methyl-D-aspartate (NMDA) receptors and reducing calcium influx in nerve cells. Magnesium prolongs the duration of analgesia without causing significant side effects. It also has a minimal impact on cardiovascular function compared to alpha-2 agonists or opioids. However, the use of magnesium is still under investigation, and its effects on different types of nerve blocks require further clinical trials 8,9.

There are many medications that can be used as adjuvants for nerve blocks, and the final decision requires the anesthesiologist to make a comparison of their physiological effects with

what is suitable for the specific clinical context. Factors to consider include side effects, duration of analgesia needed, nerve block location, and any relevant patient medical history.

References

1. Weller, R. S. & Butterworth, J. Opioids as local anesthetic adjuvants for peripheral nerve block. Tech. Reg. Anesth. Pain Manag. 8, 123–128 (2004).doi: 10.1053/j.trap.2004.03.005

2. Gola, W., Zajac, M. & Cugowski, A. Adjuvants in peripheral nerve blocks – The current state of knowledge. Anaesthesiology Intensive Therapy (2021). doi:10.5114/AIT.2020.98213

3. Andersen, J. H. et al. Alpha2-receptor agonists as adjuvants for brachial plexus nerve blocks—A systematic review with meta-analyses. Acta Anaesthesiologica Scandinavica (2022). doi:10.1111/aas.14002

4. Krishna Prasad, G. V., Khanna, S. & Jaishree, S. Review of adjuvants to local anesthetics in peripheral nerve blocks: Current and future trends. Saudi J. Anaesth. 14, 77–84 (2020). doi: 10.4103/sja.SJA_423_19

5. Chen, Z., Liu, Z., Feng, C., Jin, Y. & Zhao, X. Dexmedetomidine as an Adjuvant in Peripheral Nerve Block. Drug Des. Devel. Ther. 17, 1463–1484 (2023). doi: 10.2147/DDDT.S405294

6. Pehora, C., Pearson, A. M. E., Kaushal, A., Crawford, M. W. & Johnston, B. Dexamethasone as an adjuvant to peripheral nerve block. Cochrane Database of Systematic Reviews (2017). doi:10.1002/14651858.CD011770.pub2

7. Mikjunovikj-Derebanova, L. et al. Epinephrine and Dexamethasone as Adjuvants in Upper Extremity Peripheral Nerve Blocks in Pediatric Patients. PRILOZI (2021). doi:10.2478/prilozi-2021-0038

8. Muthiah, T. et al. Efficacy of magnesium as an adjuvant to bupivacaine in 3-in-1 nerve block for arthroscopic anterior cruciate ligament repair. Indian J. Anaesth. (2016). doi:10.4103/0019-5049.186018

9. Tresierra, S., Gilron, I. & Mizubuti, G. B. Adjuvant Medications for Peripheral Nerve Blocks. World Federation of Societies of Anaesthesiologists (2023).