Adjuvants
To add or not to add, that is the question.
The use of adjunct drugs in combination with long-acting local anesthetics (LA) may not only prolong block duration in a desirable fashion, but can also enhance block quality, reduce general anesthetic requirement, and avoid potential side effects of long-acting local anesthetics.
For a wonderful overview advocating for the routine use of adjuvants in pediatric regional anesthesia I recommend reading Per-Arne Lönnqvist's review article in Pediatric Anesthesia cited at the bottom of this page. Insightful, researched, well-argued, it provides a framework about how one might choose to practice. Much of what I touch on is directly from this article.
There is a long running debate regarding the use of adjuvants in our community. More conservatives practitioners argue that because adjuvants added to single-shot blocks may not cover the entire first 24- 48 hrs (potentially the most painful part of the post-operative period), then it doesn't warrant exposing patients to possible risks and side-effects. However, others argue that any additional time one can add to the length of the block in a child that delays the use of opioids should be considered, even if one doesn't quite make it to the ideal. Prolongation of block duration by >50% is certainly clinically relevant for improving child comfort during the often distressing early postoperative period. Current studies indicate that the use of adjuvants may prolong the length of the block by 2-3x. Bare in mind, in other areas of medicine much smaller changes may be considered clinically relevant! Furthermore, much of the current focus in pediatric anesthesiology is centered on teasing out the implications of exposure to anesthesia where a difference of only 1-2% may be at hand, albeit with obviously much, much larger implications.
To date, there are no definitive evidence-based recommendations on dosage and concentration of adjuvants in children undergoing regional anesthesia, or simply even local anesthetics for that matter. What is available is either editorial or inconclusive. For every paper one finds supporting a specific stance, one can easily find another that refutes. Many agents have been studied as adjuvants, including ketamine, neostigmine, midazolam, Mg2+, etc. These agents either lack efficacy, have unacceptable side effects, or may be potentially neurotoxic. As such, we will only focus on the agents more frequently used/studied whose benefit seems to outweigh the risk.
There is ongoing research comparing local (perineural/neuraxial) vs systemic (intravenous) adjuvant administration, mostly in adults. To date, perineural dexamethasone has been shown to be superior to intravenous administration, especially for longer acting LA agents, though this is still a contentious issue. These studies have a huge amount of heterogeneity, not only in the LA agents and amounts used, surgeries performed, but also in clinical endpoints measured, such as time to first rescue analgesic, etc. Moreover, there is also the potential for bias, such as most of the original studies have relatively small sample sizes. A recent comparison of pediatric patients undergoing knee arthroscopy found no clinical differences in analgesia.
To date, very little research has directly compared perineural dexmedetomidine vs dexamethasone as adjuncts. A recent indirect meta-analysis of 49 RCT’s comparing perineural dexmedetomidine and dexamethasone by Albrecht et al found that dexamethasone prolongs the duration of analgesia by an additional 2.5hrs. Typically, dexamethasone is a fraction of the cost of the α2 agonists. Having said that, there is also evidence that dexmedetomidine may prolong the block for slightly longer, though it does take longer to set up. Interestingly, a recent study suggested that a combination of perineural dexamethasone and dexmedetomidine may be superior to either agent used alone. This phenomenon was also seen in an earlier study.
Of the agents listed below, only clonidine and morphine PF are approved for neuraxial use. NO AGENT is approved for perineural.
Central
PF Morphine (low dose: 2-5 mcg/kg, medium dose: 5-20 mcg/kg, high dose: > 20 mcg/kg)
May last up to 24 hrs
May reduce perioperative blood loss in spinal fusion (5 mcg/kg intrathecal)
Side effects, especially with larger doses: nausea, pruritus, respiratory depression
α2 agonists: Clonidine or Dexmedetomidine
1 mcg/kg, either spinal or caudal
Both agents similarly prolong analgesia with similar side effect profiles (possible bradycardia and hypotension)
Appears to provide similar analgesia as morphine with fewer side effects
Doses > 1 mcg/kg may significantly delay emergence without any increase in analgesia
Compared to morphine, or even to each other, there may be dramatic differences in cost, even among different institutions, so one should keep costs in mind
Interestingly, there may even be similar profiles comparing neuraxial vs intravenous, or perhaps not!
Peripheral
α2 agonists (Clonidine, Dexmedetomidine)
1 mcg/kg
May be given perineural vs intravenous
Intravenous Clonidine may be superior to perineural
Dexamethasone
Mostly studied in adults
4 mg perineural may be the ideal amount in adults
Some evidence that it may actually reduce rebound pain
There are no specific guidelines or recommendations for pediatrics, though a back-calculation using 4 mg for 70 kg adult gives a dosing range of 0.05-0.1 mg/kg (up to 4 mg). Perhaps whatever is an easy amount within that range to draw up?
Lönnqvist, P.A., 2015. Adjuncts should always be used in pediatric regional anesthesia. Pediatric Anesthesia, 25(1), pp.100-106.
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Albrecht, E., Vorobeichik, L., Jacot-Guillarmod, A., Fournier, N. and Abdallah, F.W., 2018. Dexamethasone Is Superior to Dexmedetomidine as a Perineural Adjunct for Supraclavicular Brachial Plexus Block: Systematic Review and Indirect Meta-analysis. Anesthesia and analgesia.
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Woo JH, Lee HJ, Oh HW, Lee JW, Baik HJ, Kim YJ. Perineural dexamethasone reduces rebound pain after ropivacaine single injection interscalene block for arthroscopic shoulder surgery: a randomized controlled trial. Reg Anesth Pain Med. 2021 Nov;46(11):965-970. doi: 10.1136/rapm-2021-102795. Epub 2021 Sep 17. PMID: 34535548.