{
  "abstract": "Rebound pain (RP) is a clinical entity first described in 2007 by Williams and colleagues 1 qualified as acute postoperative pain occurring in the immediate hours after complete resolution of a locoregional block, and measured with a score, the Rebound Pain Score, accurately characterized by the authors like: ‘the highest Numeric Rating Scale (NRS) score recorded within the first 12 hours after the block was not providing pain relief minus the NRS score that was reported at the time the patient reported that the nerve block was providing pain relief’. Subsequently, different descriptions of this phenomenon have been given2–9 without reaching unequivocal agreement on its precise definition.10 Due to the difficulty in providing an unambiguous definition of the RP phenomenon, it is also hard to establish its incidence. A recent retrospective cohort study found that nearly half of patients experienced severe RP. This was associated with younger age, female gender, bone surgery, and no perioperative dexamethasone.7 In a recently published prospective observational study, the frequency of RP in patients undergoing Peripheral Nerve Block (PNB) and treated with multimodal analgesia and intravenous dexamethasone was 27.7%.11 The currently available scientific literature agrees that, along with a proper definition and identification of risk factors and the pathophysiological understanding of the phenomenon of the RP, multimodal analgesia and the use of adjuvants represents one of the useful tools to counteract it.6 12 13 Among these, dexamethasone is the adjuvant that has been most studied as useful drug against RP. Widely adopted for the prevention of postoperative nausea and vomiting (PONV),14 dexamethasone is considered a valuable adjuvant in multimodal analgesia because of its antinflammatory and immunomodulatory properties.15 A recent metanalysis on the use of dexamethasone compared with placebo concludes that its use reduces the incidence of RP.16 17 In addition a network metanalysis of 14 randomized controlled trials (RCTs) with a sample size of about 1000 patients comparing intravenous dexamethasone, perineural dexamethasone, and placebo shows moderate certainty evidence that intravenous dexamethasone is superior in reducing the incidence of RP compared with placebo or perineural dexamethasone, and it was not associated with postoperative hyperglycemia or increased risk of infection.18 The main limitations of these studies are due to the low number of RCTs published on the topic, which often consider extremely wide dexamethasone dose ranges. There is evidence that high doses of dexamethasone in the treatment of acute postoperative pain have an opioid sparing effect at 24 hours after surgery, however, there are still no adequate data testing their safety in terms of adverse effects such as hyperglycemia, prolongation of surgical wound healing time, infectious complications, and sleep disturbances.19 The role of ketamine in preventing RP has been evaluated in three RCTs,20–22 of these, the study by Touil and colleagues21 analyzing about 100 patients undergoing PNB of the upper extremity for day case surgery and treated with intravenous bolus of preoperative ketamine in comparison to placebo finds no difference in terms of incidence of RP. Ketamine, a non-selective inhibitor of N-methyl-D-aspartate receptors that displays analgesic, antihyperalgesic, and antinflammatory properties at dosages of 0.3 mg/kg intravenously does not appear to play a role in the incidence of RP suggesting that underlying the pathophysiological mechanisms of RP are no central sensitization mechanisms. In contrast, RP cases correlated significantly with higher pain catastrophizing scores. These results need to be confirmed by larger sample studies and they could also be explained by ketamine dosages which were kept extremely low in the intervention group.22 23 However, this study highlights the possibility that beyond the appropriate multimodal analgesic treatments, catastrophizing or exaggerated negative mental attitude also plays a notable role in the incidence of RP suggesting that in addition to adherence to multimodal treatments, patient-centered therapeutic approaches are necessary to combat RP. Little evidence still exists on the use of dexmedetomidine and perineural clonidine on the prevention of RP.9 24 Significantly the administration of hydromorphone at 6 hours after the performance of PNB had no effect on the incidence of RP, these results were explained by the finding that the timing of action of hydromorphone did not coincide with the complete resolution of the block still partially active, and considering that the population studied was not involved in bone surgery in which classically RP has higher incidence.25 In conclusion, the pathophysiological mechanisms underlying RP are complex, not fully known, and the variability in estimating its incidence is also due to the difficulty in establishing a common unambiguous definition. Within the chapter of multimodal analgesia, the most consistent data regarding the reduction of the incidence of RP are in favor of the use of intravenous dexamethasone, future treatment approaches should consider, in addition to risk factor limitation, specific patient-centered strategies not yet fully explored.References Williams B, Bottegal M, Kentor M, et al. Rebound pain scores as a function of femoral nerve block duration after anterior cruciate ligament reconstruction: retrospective analysis of a prospective, randomized clinical trial. Regional Anesthesia and Pain Medicine 2007;32:186–92. doi: 10.1016/j.rapm.2006.10.011.Dada O, Gonzalez Zacarias A, Ongaigui C, et al. Does rebound pain after peripheral nerve block for orthopedic surgery impact postoperative analgesia and opioid consumption? A narrative review. IJERPH. 2019;16:3257. doi: 10.3390/ijerph16183257.Muñoz-Leyva F, Cubillos J, Chin KJ. Managing rebound pain after regional anesthesia. Korean J Anesthesiol. 2020;73:372–83. doi: 10.4097/kja.20436.Kolarczyk LM, Williams BA. Transient heat hyperalgesia during resolution of ropivacaine sciatic nerve block in the rat. Regional Anesthesia and Pain Medicine 2011;36:220–4. doi: 10.1097/AAP.0b013e3182176f5aGalos DK, Taormina DP, Crespo A, et al. Does brachial plexus blockade result in improved pain scores after distal radius fracture fixation? A randomized trial. Clinical Orthopaedics & Related Research 2016;474:1247–54. doi: 10.1007/s11999-016-4735-1.Lavand’homme P. Rebound pain after regional anesthesia in the ambulatory patient. Current Opinion in Anaesthesiology 2018;31:679–84. doi: 10.1097/ACO.0000000000000651Barry GS, Bailey JG, Sardinha J, et al. Factors associated with rebound pain after peripheral nerve block for ambulatory surgery. British Journal of Anaesthesia 2021;126:862–71. doi: 10.1016/j.bja.2020.10.035.Williams BA. Forecast for perineural analgesia procedures for ambulatory surgery of the knee, foot, and ankle: applying patient-centered paradigm shifts. International Anesthesiology Clinics 2012;50:126–42. doi: 10.1097/AIA.0b013e31821a00d0Nobre LV, Cunha GP, Sousa PCCBD, et al. Bloqueio de nervos periféricos e dor rebote: revisão de literatura. Brazilian Journal of Anesthesiology 2019;69:587–93. doi: 10.1016/j.bjan.2019.05.001Hamilton DL. Rebound pain: distinct pain phenomenon or nonentity? British Journal of Anaesthesia 2021;126:761–3. doi: 10.1016/j.bja.2020.12.034.Atar F, Özkan SipahioĞlu F, Karaca Akaslan F, et al. Frequency of rebound pain and related factors in a multimodal regimen including systemic dexamethasone and dexmedetomidine. Anaesthesiologie 2025;74:148–55. doi: 10.1007/s00101-025-01502-zYin W, Luo D, Mi H, et al. Rebound pain after peripheral nerve block: a review. Drugs Published Online First: 22 May 2025. doi: 10.1007/s40265-025-02196-8.Uppal V. Rebound pain after peripheral nerve blocks: end of the honeymoon period. ASA Monitor. 2024;88:1–9. doi: 10.1097/01.ASM.0001016784.78910.8cWeibel S, Rücker G, Eberhart LH, et al. Drugs for preventing postoperative nausea and vomiting in adults after general anaesthesia: a network meta-analysis. Cochrane Database of Systematic Reviews 2020;2020. doi: 10.1002/14651858.CD012859.pub2.Myles PS, Corcoran T. Benefits and risks of dexamethasone in noncardiac surgery. Anesthesiology 2021;135:895–903. doi: 10.1097/ALN.0000000000003898Singh PM, Borle A, Panwar R, et al. Perioperative antiemetic efficacy of dexamethasone versus 5-HT3 receptor antagonists: a meta-analysis and trial sequential analysis of randomized controlled trials. Eur J Clin Pharmacol. 2018;74:1201–14. doi: 10.1007/s00228-018-2495-4.Yang Z-S, Lai H-C, Jhou H-J, et al. Rebound pain prevention after peripheral nerve block: a network meta-analysis comparing intravenous, perineural dexamethasone, and control. Journal of Clinical Anesthesia 2024;99:111657. doi: 10.1016/j.jclinane.2024.111657.Makkar JK, Singh NP, Khurana BJK, et al. Efficacy of different routes of dexamethasone administration for preventing rebound pain following peripheral nerve blocks in adult surgical patients: a systematic review and network meta-analysis. Anaesthesia 2025;80:704–12. doi: 10.1111/anae.16566.Laconi G, Coppens S, Roofthooft E, et al. High dose glucocorticoids for treatment of postoperative pain: a systematic review of the literature and meta-analysis. Journal of Clinical Anesthesia 2024;93:111352. doi: 10.1016/j.jclinane.2023.111352Zhu T, Gao Y, Xu X, et al. Effect of ketamine added to ropivacaine in nerve block for postoperative pain management in patients undergoing anterior cruciate ligament reconstruction: a randomized trial. Clinical Therapeutics 2020;42:882–91. doi: 10.1016/j.clinthera.2020.03.004.Touil N, Pavlopoulou A, Barbier O, et al. Evaluation of intraoperative ketamine on the prevention of severe rebound pain upon cessation of peripheral nerve block: a prospective randomised, double-blind, placebo-controlled study. British Journal of Anaesthesia 2022;128:734–41. doi: 10.1016/j.bja.2021.11.043.Li Q, Tian S, Zhang L, et al. S-Ketamine reduces the risk of rebound pain in patients following total knee arthroplasty: a randomized controlled trial. DDDT. 2025;19:2315–27. doi: 10.2147/DDDT.S515741.Jen TTH, Victor AD, Ke JXC. Role of intraoperative ketamine in preventing severe rebound pain for patients undergoing ambulatory upper extremity surgery. Comment on Br J Anaesth 2022;128:734–41. British Journal of Anaesthesia 2022;129:e32–3. doi: 10.1016/j.bja.2022.04.021.Hwang J-T, Jang JS, Lee JJ, et al. Dexmedetomidine combined with interscalene brachial plexus block has a synergistic effect on relieving postoperative pain after arthroscopic rotator cuff repair. Knee Surg Sports Traumatol Arthrosc. 2020;28:2343–53. doi: 10.1007/s00167-019-05799-3.Uppal V, Barry G, Ke JXC, et al. Reducing rebound pain severity after arthroscopic shoulder surgery under general anesthesia and interscalene block: a two-centre randomized controlled trial of pre-emptive opioid treatment compared with placebo. Can J Anesth/J Can Anesth. 2024;71:773–83. doi: 10.1007/s12630-023-02594-0.",
  "authors": [
    {
      "affiliations": [
        "Department of Anesthesia, Intensive Care, and Pain Management, University Hospital of Ferrara Italy, Ferrara, Italy"
      ],
      "name": "Giulia Laconi"
    }
  ],
  "title": "FT35 Multimodals to avoid rebound pain",
  "uid": "69228e86-5ed1-5122-aa6c-af22046e2dfd"
}