Tag Archives: adjuvants

Anesthesiology, Medical Education, Pain Medicine, Regional Anesthesiology

Extending Nerve Block Pain Relief after Surgery: Review of the Evidence

nerve firingNerve blocks (also referred to as “regional anesthesia”) offer patients many potential advantages in the immediate postoperative period such as decreased pain, nausea and vomiting, and time spent in the recovery room (1,2). However, these beneficial effects are time-limited and do not last beyond the duration of the block (2). While the clinical effects of nerve blocks typically last long enough for patients to meet discharge eligibility from recovery and avoid hospitalization for pain control (3), these results can be easily negated if patients’ pain or opioid-related side effects warrant a return trip to the hospital and readmission following block resolution (4). Thus, extending block duration to provide longer-term, site-specific analgesia for patients on an ambulatory basis has been a high research priority. What options are currently available?

Continuous Peripheral Nerve Blocks

Continuous peripheral nerve block (CPNB) techniques (also known as perineural catheters) permit delivery of local anesthetic solutions to the site of a peripheral nerve on an ongoing basis (5). Portable infusion devices can deliver a solution of plain local anesthetic for days after surgery, often with the ability to titrate the dose up and down or even stop the infusion temporarily when patients feel too numb (6,7). In a meta-analysis comparing CPNB to single-injection peripheral nerve blocks, CPNB results in lower patient-reported worst pain scores and pain scores at rest on postoperative day (POD) 0, 1, and 2 (8). Patients who receive CPNB also experience less nausea, consume less opioids, sleep better, and are more satisfied with pain management (8). We also know how CPNB works: local anesthetic medication interrupts nerve transmission, so patients experience decreased sensation.

Managing CPNB patients (especially at home) can sometimes be challenging, and not all patients are good candidates for outpatient perineural infusion (7). Patients must have a reliable means of follow-up and should have a caretaker at home for at least the first night after surgery (7). A health care provider must be available at all times to manage common issues associated with CPNB and call patients once daily to assess for analgesic efficacy and side effects (9). Patients, especially those undergoing lower extremity surgery, and their caretakers should receive clear instructions regarding the care of their infusion device and catheter as well as their anesthetized extremities (10,11) including fall precautions (12,13).

Although the optimal duration for CPNB is unknown, 2 to 7 days has been reported for orthopedic inpatients (14) with durations as long as 34 days under special circumstances (15). At the completion of the local anesthetic infusion, perineural catheters must be removed. To date, CPNB is the only technique that offers patients the longest potential duration of block paired with the ability to titrate to the desired level of block.

Despite more than a decade of published data supporting CPNB for extending the duration of postoperative pain control, adoption of these techniques is not universal. Many of the issues are arguably system-based, and the lack of a “block” room (16) or time pressure (17) may be responsible. However, lack of training in these techniques may also be a factor (18) or negative experiences with failed placement attempts using traditional techniques (19).

Adjuvants to Local Anesthetic Solutions for Single-Injection Peripheral Nerve Blocks

For nerve blocks intended to last 1-2 days, there are a few options.  Long-acting local anesthetics (e.g., bupivacaine, levobupivacaine, and ropivacaine) generally provide analgesia of similar duration for 24 hours or less (20-23). Several different drugs have been investigated for their potential to extend single-injection peripheral nerve block duration when added to local anesthetic solutions. Epinephrine when added to local anesthetic solutions provides vasoconstriction to decrease uptake but has little or no clinical effect on the duration of longer-acting local anesthetics (24). Opioids in general do not provide additional benefits in terms of duration (25) except for buprenorphine (26) although how it works is unclear. To date, there are insufficient data to support the addition of tramadol or neostigmine to local anesthetic solutions (25). Of the available adjuvants, clonidine has been demonstrated in clinical studies and systematic reviews to extend the duration of analgesia for intermediate-acting local anesthetics (e.g., mepivacaine) with few side effects in doses up to 150 mcg but probably do not extend long-acting local anesthetics (25,27). There has been increasing interest in dexamethasone as an adjuvant to local anesthetic solutions based on clinical reports of extended duration when added to intermediate-acting local anesthetics (28,29). The mechanism is not well understood and may be less pronounced with long-acting local anesthetics; one study reported block durations of only 22 hours with dexamethasone added to either ropivacaine or bupivacaine (30). Giving dexamethasone intravenously may actually produce the same effect (31). Caution is warranted when experimenting with adjuvant mixtures that have not been specifically approved for nerve blocks (i.e., “off-label” use) as many of the usual FDA safeguards have not been performed, and these drugs may contribute to neurotoxicity or other side effects not yet known.

Novel Extended-Duration Local Anesthetics

There has been interest in liposomal formulations of extended-release bupivacaine for regional anesthesia for over two decades (32,33). A recent formulation consisting of bupivacaine encapsulated in multivesicular liposomes to produce slow release is FDA-approved for local infiltration (34) but not yet for nerve blocks although this is expected soon. A nerve block with liposomal bupivacaine can be expected to last 1-3 days. Initial nerve block studies in animals suggest a lower maximum serum concentration with the liposomal formulation compared to plain bupivacaine (35)–unless co-administered with lidocaine which facilitates release of liposomal bupivacaine (36)–and epidural administration in human volunteers more than doubles duration of sensory block (37). Once it receives FDA approval, I expect many comparative studies versus CPNB for postoperative analgesia. There are still concerns regarding local anesthetic systemic toxicity with liposomal bupivacaine as well as prolonged motor block and unpleasant numbness given the drug’s long-lasting effects. In addition, there is no option for “giving more” to augment a block in the event of inadequate pain relief.

In summary, there are currently few options to extend the duration of regional analgesia at home beyond the one day expected from most single-injection nerve blocks. CPNB with plain local anesthetic perineural infusion is the most established way to provide days of postoperative pain control and allows titration, but training in insertion techniques and a system to manage ambulatory CPNB patients are necessary. Adjuvants or liposomal formulations of local anesthetics may offer potential options for limited extension of block duration, but further studies regarding efficacy and safety for regional anesthesia as well as comparative-effectiveness versus CPNB are necessary. For major surgery like total knee replacement, block duration of several days may be optimal (38).

References

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