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Postoperative pain is one of the main pre-operative concerns for surgical patients. 1 2 Postoperative pain is a major problem, and most patients will experience moderate to severe pain within the first 24 hours postoperatively.3 The risks of poorly controlled postoperative pain are well established and include delayed recovery and discharge from hospital, reduced quality of life, prolongation of opioid use, and risk of developing chronic postoperative pain.4 Nerve blocks provide the ability to control postoperative pain by shutting down the transmission of signals from peripheral nerves, including pain signals. If a nerve block fully covers the surgical area, postoperative pain is eliminated for the duration of the nerve block. However, conventional long-acting local anaesthetics will only provide a duration of 8 to 14 hours. Therefore, many drugs utilised in anaesthesiologic care has been tested as means for providing increased postoperative analgesia when used in combination with a peripheral nerve block.5–7 Specifically, many of the drugs have been mixed with a local anaesthetic and injected perineurally, and have therefore been called ‘adjuncts’ to nerve blocks. Most drugs have not been able to increase block duration to a clinically meaningful degree, and others have been associated with an increased risk of adverse events, outweighing beneficial effects. The two most promising adjuncts to peripheral nerve blocks are dexamethasone and dexmedetomidine.Dexamethasone Dexamethasone is a glucocorticoid with potent anti-inflammatory properties. It is an old drug that is used for a wide range of indications with a very well-established safety profile. Importantly, a single perioperative dose of dexamethasone has not been found to increase the risk of important adverse events such as infections, impaired wound healing, or clinically important changes in plasma glucose levels. 8–14 In the context of increasing block duration, dexamethasone has been administered perineurally, intravenously, and orally. Systematic reviews of randomised trials have consistently showed that dexamethasone can increase block duration by up to 7 hours.15–20 There is an on-going debate on whether dexamethasone should be administered perineurally or intravenously. Research has indicated that the perineural route of administration might increase block duration by 1 to 3 hours when compared with the intravenous route.16 17 21–25 However, the potential increase in block duration with perineural versus intravenous dexamethasone does not seem to be clinically important. A recent trial investigated the effects of combining intravenous and perineural dexamethasone and found the duration of the block to be similar to intravenous dexamethasone alone.26 Furthermore, a trial in healthy volunteers employing a design controlling for the systemic effects of perineural administration did not find convincing evidence of an important perineural mechanism of action in the absence of inflammation from trauma or surgery.27 The potential effects of perineural dexamethasone also needs to be considered in the light of dexamethasone potentially being pharmacologically incompatible with local anaesthetics,28 29 not being approved for perineural administration, and that a biological perineural mechanism of action has not been proven.Rebound pain is severe pain usually defined as pain at or above 7 out of 10 on the Numerical Rating Scale and occurs at block cessation. Adjunct dexamethasone reduces the risk of rebound pain,30 but a recent systematic review with network meta-analysis indicated that intravenous dexamethasone is more efficient in reducing the risk of rebound pain than perineural dexamethasone.31 Only one trial has investigated oral dexamethasone (24 mg vs 12 mg vs placebo) as an adjunct to infraclavicular brachial plexus blocks and found oral dexamethasone to increase time to first pain by 7-hours when compared with placebo, which is similar to perineural and intravenous administration in other trials.32 However, the oral route of administration is yet to be compared to intravenous and perineural administration in a clinical trial.Dexmedetomidine Dexmedetomidine has also been found to be effective in prolonging block duration. 33 Contrary to dexamethasone, research has suggested that an important perineural mechanism of action exists for dexmedetomidine. A trial in healthy volunteers controlling for the systemic effects of perineurally administered dexmedetomidine showed perineural administration to be superior to that of systemic administration.34 Randomised trials have also showed perineural administration to be superior to perineural administration.33 Dexmedetomidine whether administered perineurally or intravenously is associated with hypotension, bradycardia, and sedation, potentially outweighing the beneficial effects on block duration and limiting its use in ambulatory surgery.33 Dexamethasone Versus Dexmedetomidine Systematic reviews with meta-analysis of randomised trials comparing dexamethasone and dexmedetomidine found dexamethasone to be superior to dexmedetomidine in increasing block duration. 22 Therefore, given that dexamethasone increases block duration more than dexmedetomidine and that a single dose of perioperative dexamethasone is not associated with adverse effects, dexamethasone is favoured over dexmedetomidine as an adjunct to peripheral nerve blocks.Combining Dexamethasone and DexmedetomidineAs the mechanisms of action are different, the combination of dexamethasone and dexmedetomidine has been hypothesized to have additive effects on block duration. Several trials have investigated the effects of combining dexamethasone and dexmedetomidine. Recent trials have consistently showed that the combination of dexamethasone and dexmedetomidine is not superior to dexamethasone alone.7 35 Therefore, the current evidence supports the use of dexamethasone as the sole agent for increasing block duration.Other Adjuncts Several other perineural adjuncts have been investigated, including midazolam, various opioids (morphine, hydromorphone, tramadol, fentanyl), neostigmine, and ketamine. However, they have all been associated with lack of effectiveness. 36 Epinephrine is added to some local anaesthetics by the manufacturers, but does not increase block duration by more than 1 hour.37 Buprenorphine effectively increases block duration by up to 8 hours, but also significantly increases the risk of pruritus and post-operative nausea and vomiting.38 Clonidine is less effective than dexmedetomidine in increasing block duration and also results in adverse effects such as hypotension, bradycardia, and sedation.39 Magnesium only increases block duration by up to 2 hours.40 Conclusion In summary, dexamethasone should be the primary agent of choice for increasing block duration. There is no additional benefit of combining dexamethasone and dexmedetomidine. Intravenous dexamethasone is currently to be preferred over perineural dexamethasone. Intravenous dexamethasone should be administered in doses of 0.1 to 0.2 mg/kg. 36 References Apfelbaum JL, Chen C, Mehta SS, et al. 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