Perineural dexamethasone is an effective adjuvant used to prolong the duration of the sensory block after regional anaesthesia[16]. However, whether it can alleviate the rebound phenomenon after nerve block is remained to be investigated. Our study demonstrated that when being added into 0.375% ropivacaine, 8 mg dexamethasone effectively reduced the incidence of rebound pain in patients receiving ORIF for upper extremity fracture under single-injection nerve block. Dexamethasone addition not only prolonged the duration of sensory block, reduced the opioid consumption in 24 h after the block administration; it also decreased the pain intensity at the point patients described it as the most severe pain after the block. Patients received perineural dexamethasone addition reported better sleep quality on the night of surgery and higher satisfaction to the postoperative pain therapy.
Rebound pain following single-shot nerve block is a clinically relevant but less valued phenomenon which even diminishes the real benefit of peripheral nerve block in some surgeries[7, 8, 17].Patients undergoing surgical repair of distal radius fractures experienced different pain profile after general anaesthesia compared with a peripheral nerve block. Although patients with brachial plexus block had less pain immediately after the procedure, 12 h to 24 h later when the block wore off, their pain was higher than those in the general anaesthetic group[10].
The mechanism of rebound pain remains poorly understood. Fading of nerve block could not explain that there are a certain number of patients who do not experience the outbreak of excruciating pain during the block wear off. It is also noticed that the rebound pain does not respond to intravenous opioids administration[6]. We found that although we provided a background infusion of a high lipid-soluble opioid-sufentanil to maintain a steady blood concentration and a relatively short lockout time of 6 min in PCA, the patients who suffered from rebound pain still could not get relieved by PCA administration. In Williams’ study [18] some patients described rebound pain as an intense burning pain initially as the nerve block resolves. This evidence might suggest the neuropathic instead of a nociceptive component of rebound pain after nerve block. Kolarczyk’s study on rats[19] found that 0.5%ropivacaine induced transient heat hyperalgesia in the setting of resolved mechanical analgesia. Early studies have also suggested that local anaesthetics can cause nerve swelling and alter the permeability of the outer membrane of the nerve, leading to abnormal nerve conduction[14]. Therefore, local anaesthetic toxicity and the proinflammatory effect of local anaesthetics[20] might contribute to the occurrence of rebound pain.
Dexamethasone is a highly potent long-acting glucocorticoid. It improves the quality and prolongs the duration of PNB over LA alone[21]. The mechanism is not fully understood but suggested possible mechanism includes attenuating the release of inflammatory mediators, reducing ectopic neuronal discharge, and inhibiting potassium channel-mediated discharge of nociceptive C-fiber[22–24]. An K et al. found that perineural dexamethasone added to a clinical concentration of bupivacaine prevent the bupivacaine-induced reversible neurotoxicity and short-term "rebound hyperalgesia" in mouse sciatic nerve block model [15]. We demonstrated that adding 8 mg dexamethasone to 0.375% ropivacaine reduced the incidence of rebound pain from 48.8–11.1% after ORIF of upper extremity fracture under single-shot nerve block.
In Brian Williams’s retrospective study[25] on the additives to a single-injection nerve block, 2 mg perineural dexamethasone addition provides favourable rebound pain profile than dosing of “other than 2mg” (i.e., no dexamethasone or 4 mg total perineural dexamethasone). We chose 8 mg because it is a commonly selected dosage in the study regarding the effect of dexamethasone as an adjuvant to local anaesthetics[26]. We did not investigate the dose-effect of dexamethasone addition. Whether a lower dosage of dexamethasone provides the same or better rebound pain profile needs to be investigated, especially in some population, such as diabetic patients.
Rune S et al. prospectively followed 21 patients scheduled for acute open reduction and internal fixation rebound phenomenon was less pronounced in patients older than 60 years old, whereas most of them suffered from moderate pain (NRS 4–6) during block effect wears off[8]. We did not find the association between rebound pain incidence and age in the correlation study. However, if grouping the patients by > 60 yrs or ≤ 60 yrs, the patients younger than 60 years old thus possessed a relatively higher incidence of rebound pain (31% vs 23%). Whether the pain trajectory after nerve block changes gradually with ageing or display a drastic change in a certain age needs to be clarified in the future study.
It is challenging to define rebound pain after nerve block. Williams BA et al[18]described rebound pain scores as a quantifiable difference between the highest NRS score after the nerve block wore off and the last NRS score when the nerve block was still providing pain relief. From our preliminary results, under most circumstances, rebound pain happens all in a sudden, at night or elicited by movements. Based on the findings from our preliminary observational study, we empirically define the rebound pain as “severe pain (NRS > 7) which breaks out in 48 hours after single-shot nerve block, whether at rest or elicited by movement, and cannot be relieved by multiple PCIA bolus in 30 minutes; if the pain occurs at the sleep time, it wakes up the patients and makes them difficult to go back to sleep”. Lavand'homme P[17] gave a detailed description of the definition and characteristics of rebound pain. Our definition is similar to that of Lavand'homme P except that we extend the time limit to 48 hours because dexamethasone addition elongates the block duration. We failed to find a unique description of the pain character as burning or aching, so we eliminated the pain character as one of the criteria. Since the rebound phenomenon is hard to detect during regular follow up, we gave the diagnosis based on the patients' self-report and pain diary. Further studies are needed to unify the definition of rebound pain to facilitate more randomized trials in this area.
Although dexamethasone is one of the most common additives to a nerve block, there are still some safety concerns. Desmet[27] reported an increase in blood glucose concentrations in the group with dexamethasone, which needed insulin therapy. We found that the blood glucose at 6 h after the surgery increased but no statistical difference between the two groups and none of our patients required insulin therapy. This might because we ruled out the patients with diabetes.
There are limitations to our study. We did not investigate the effect of intravenous dexamethasone on rebound pain occurrence. So we cannot decide the reduction of rebound phenomenon is the perineural or systemic effect from absorption of dexamethasone. Comparison between intravenous and perineural dexamethasone showed conflict results on whether the prolongation of nerve block is the systemic or perineural origin. Results from the meta-analysis showed that for bupivacaine, perineural dexamethasone addition leads to a statistically significant prolongation of analgesic duration by 21% compared with intravenous administration. While for ropivacaine, the mean duration of analgesia was increased by 12% with perineural dexamethasone compared with systemic dexamethasone, which did not reach statistical significance. The author concluded that the finding of equivalence between both routes of administration remains underpowered for ropivacaine, and a total of 1124 patients would be needed before suggesting a definitive conclusion[28]. Because intravenous dexamethasone has a strong anti-inflammatory effect and perineural administration is still off-label, further study is necessary to investigate the effect of intravenous dexamethasone on incidence of rebound pain.