Rebound Pain After Peripheral Nerve Blocks: End of the Honeymoon Period

When compared with general anesthesia (GA), patients undergoing surgery solely under peripheral nerve blocks (PNBs) are more likely to have improved short-term postoperative pain control, less nausea and vomiting, early discharge from the postanesthesia care unit and hospital, and overall improved patient satisfaction (Br J Anaesth 2015;114:728-45; BJA Educ 2018;18:52-6).

Single-injection PNBs provide excellent analgesia with minimal side effects for six to 10 hours after surgery. Nevertheless, it is estimated that approximately 50% of patients experience severe pain after a single injection nerve block wears off. This sudden increased pain after the resolution of the local anesthetic effect is often referred to as “rebound pain.” Rebound pain may not only reduce satisfaction with perioperative care but also increase health care workload and cost, with patients needing to return to the hospital (or failing to go home) for its management.

Rebound pain is not a new entity but is increasingly recognized as a significant clinical problem. A recent international Delphi study seeking to identify research priorities in regional anesthesia identified the question “How can we best manage pain as regional anesthesia wears off?” as the top priority question (Br J Anaesth March 2024).

Over the last decade or so, various authors have attempted to define rebound pain. Streb et al. collated nine definitions of “rebound pain” (Anaesthesiologie 2022;71:638-45). Most definitions for rebound pain share a common theme, describing it as the unmasking of surgical pain when the effects of the nerve block wear off (Curr Opin Anaesthesiol 2018;31:679-84). It is unlikely to be a state of hyperalgesia, as suggested by some authors (Int J Environ Res Public Health 2019;16:3257). In simple terms, the period during which the PNB is effective can be viewed as a postsurgery honeymoon phase, characterized by minimal pain and side effects. Blocks resolve with a sudden increase in pain, described as “rebound pain,” signalling the end of the postoperative honeymoon period.

Several factors, including patient, anesthetic, and surgical variables, have been linked to a higher incidence of rebound pain. Barry et al. categorized these factors as modifiable and nonmodifiable factors (Br J Anaesth 2021;126:862-71). Understanding these factors may allow targeted care of at-risk patients. The nonmodifiable factors include younger age, female sex, bony surgery, and possibly upper-limb surgery. Of these, bony surgery was the strongest predictor of rebound pain. In the modifiable factor, the absence of dexamethasone was associated with a higher incidence of rebound pain (Br J Anaesth 2021;126:862-71).

Some possible strategies for the prevention and management of rebound pain are shown in the Figure. A number of review articles have assessed the evidence on some of the above interventions to prevent and manage rebound pain after nerve blocks (Curr Pain Headache Rep 2023;27:449-54; Korean J Anesthesiol 2020;73:372-83). However, the evidence in this area is rapidly evolving. A PubMed search on January 23, 2024, found several additional papers on the topic. Among all the interventions, intravenous dexamethasone use has been extensively studied.

A recent systematic review pooled data from seven randomized clinical trials assessing prophylactic dexamethasone for rebound pain after PNBs and suggests that both intravenous and perineural dexamethasone reduce the incidence of rebound pain after a PNB, with a number needed to treat of 2.8 (Br J Anaesth October 2023). Intravenous dexamethasone may have a dose-effect relationship for reducing rebound pain. The study using the highest dose of dexamethasone (Holmberg 2020) showed the most impressive effect size among the four randomized clinical trials using I.V. dexamethasone (Anaesthesia 2020;75:1448-60; J Pain Res 2023;16:1127-36; Hernia 2023;27:1571-80; Ann Saudi Med 2023;43:339-47). However, we cannot definitively reach this conclusion as the data are likely underpowered. Indeed, an observational study did not find that a high dose of dexamethasone (more than 0.1 mg/kg) was more effective than a lower dose of dexamethasone (J Clin Med 2023;12:4310). Nevertheless, it is well known that dexamethasone in a dose of less than 0.1 mg/kg is unlikely to have analgesic effects (Br J Anaesth 2011;107:362-71).

Four randomized clinical trials evaluated the perineural use of dexamethasone to reduce rebound pain, with three studies showing positive results (Reg Anesth Pain Med 2021;46:965-70; BMC Anesthesiol 2021;21:47; Clin Orthop Relat Res 2023;481:1966-74). The one negative study used a lower dose (3.3 mg) of dexamethasone perineurally (J Shoulder Elbow Surg 2020;29:1751-57). Finally, a study comparing I.V. and perineural dexamethasone head-to-head found no distinct advantage of perineural dexamethasone over I.V. route (J Korean Med Sci 2023;38:e183).

Regarding other adjuvants, two studies evaluated perineural dexmedetomidine and found it reduces pain in the first 12 hours after the block (Knee Surg Sports Traumatol Arthrosc 2020;28:2343-53; Knee Surg Sports Traumatol Arthrosc 2021;29:4022-31). Nevertheless, the moderate analgesic efficacy of perineural dexmedetomidine must be balanced against possible side effects such as bradycardia and sedation. Perineural, but not I.V., ketamine appears to reduce rebound pain (Clin Ther 2020;42:882-91; Br J Anaesth 2022;128:734-41). However, perineural ketamine use is off-label. Finally, there is insufficient evidence to support the routine use of liposomal bupivacaine to reduce rebound pain after nerve blocks (J Bone Joint Surg Am 2018;100:1373-8).

The timing of a dose of a potent opioid to coincide with the time of PNB resolution has been suggested as one of the strategies to reduce rebound pain. However, a two-center randomized clinical trial evaluating oral hydromorphone given six hours after interscalene block did not reduce the severity of rebound pain postoperatively compared with placebo in patients undergoing arthroscopic shoulder surgery (Can J Anaest October 2023). Considering that rebound pain usually occurs much later than six hours after the block, future studies may evaluate timing the opioid around 10 to 12 hours after the nerve block.

Using continuous PNBs (CPNBs) to prolong the duration of PNBs to match the duration of severe surgical pain appears to be the most intuitive solution to reducing the incidence and severity of rebound pain postoperatively. However, clinical trials have shown somewhat mixed results (Reg Anesth Pain Med 2007;32:186-92; J Orthop Trauma 2015;29:393-8; J Orthop Trauma 2018;32:22-6; J Shoulder Elbow Surg 2018;27:1243-50; Korean J Anesthesiol 2023;76:559-66). This might be due to CPNBs being technically more challenging and resource-intensive or because of lower infusion dose regimens used for shorter postoperative periods in some studies.

In summary, addressing rebound pain post-block necessitates a multifaceted approach involving various preventive and management strategies that include identifying individuals at risk. Patients should receive a thorough education on implementing robust multimodal analgesia (if not contraindicated), particularly before the resolution of nerve blocks. Clinicians should consider CPNBs for patients at the highest risk of experiencing rebound pain (resource permitting). In the context of a single-injection block, clinicians should use a higher dose of I.V. dexamethasone if there are no contraindications. When surgery is planned solely under PNB with sedation, dexamethasone should be given slowly postsedation to mitigate potential side effects such as flushing and perineal itching associated with dexamethasone (Can J Anaesth 2003;50:749-50). In conclusion, clinicians should not hesitate to use PNBs out of concern for rebound pain, much like a married couple should not forego their honeymoon out of fear of potential challenges that may arise afterward.