Novel Techniques and Local Anesthetics for Perioperative Pain Management

Abstract

Careful perioperative pain management is crucial for good patient outcomes after surgery, as poorly controlled pain interferes with the ability of patients to recover to normal baseline function and increases postoperative morbidity and mortality. Although opioids have been the mainstay for treating postoperative pain, there has been a shift in favor of a multimodal analgesic approach, including regional anesthesia, as a way to circumvent opioid-related adverse events (e.g. nausea and vomiting, respiratory depression, sedation). In this chapter, we present an update on several recently developed regional anesthetic techniques, local anesthetic medications, as well as nerve block adjuncts with the potential to improve pain management in the perioperative setting. With more future studies, these novel methods may be incorporated into postsurgical recovery protocols and provide the opportunity to improve patient outcomes.

1. Introduction

Prevention, treatment, and management of pain are crucial to delivering good outcomes for patients undergoing surgery. Poorly controlled pain from surgeries can trigger physiological stress responses that damage body organs while causing psychological and emotional distress to patients, thereby increasing postoperative morbidity and mortality [1]. Additionally, inadequate pain control may also interfere with the ability of patients to participate in rehabilitation activities, prolong length of hospitalization, and raise the overall cost of healthcare [2, 3]. Historically, opioids have been the mainstay for postoperative pain. However, to avoid the myriad of opioid-related adverse events (e.g. respiratory depression, sedation, vomiting), there has been a shift in favor of multimodal analgesia in recent years to combine different classes of analgesics and create a synergistic effect to alleviate pain [1, 4]. One major component of multimodal analgesia is regional anesthesia and nerve blocks to reduce perioperative pain. In this chapter, we present several novel regional anesthesia techniques, local anesthetic medications, and nerve block adjuncts developed in recent years that offer unique advantages for pain management in the perioperative setting. Further future research to investigate these techniques and medications will be critical for developing evidence-based guidelines and protocols in order to improve patient outcomes in surgical settings.

2. Erector spinae plane block (ESPB)

The erector spinae plane block (ESPB) is a relatively novel regional technique for acute and chronic pain management which delivers local anesthetics between the thoracic transverse process and the erector spinae muscles [5, 6]. The ESPB was first described by Forero et al. in 2016 as an ultrasound-guided interfascial plane block that not only produces effective multi-dermatomal analgesia for severe chronic neuropathic pain from metastatic disease of the ribs and rib fractures, but also improves postoperative pain in patients undergoing video-assisted thoracoscopic lobectomies [5]. Since then, the ESPB has gained popularity for its simplicity, safety, and ease of delivery. Its use for perioperative pain management has expanded to a wide variety of surgeries, including thoracotomies [7], breast surgeries [7, 8], ventral hernia repair [9], percutaneous nephrolithotomies [10], and even lumbar fusion [11, 12, 13].

2.1 Anatomy and technique

The ESPB mainly involves the deep intrinsic back muscles, which are divided into three layers: spinotransversales (superficial), erector spinae muscles (intermediate), and transversospinales (deep) [6, 14]. The spinotransversales layer allows for neck extension and head rotation, whereas the intermediate erector spinae muscles are a complex muscular group that connects the spinous processes, ribs, and transverse processes from each side of the spine. Finally, the transversospinales layer deep to the erector spinae muscles joins the transverse processes to the spinous processes [6, 14].

As each upper thoracic spinal nerve exits the intervertebral foramen, it separates into the dorsal and ventral rami. The dorsal ramus runs posteriorly into the erector spinae muscle before splitting to lateral and medial branches. The medial branch continues posteriorly to supply a posterior cutaneous branch for the back of the chest. On the other hand, the ventral ramus curves laterally to become the intercostal nerve. It gives rise to the lateral cutaneous branch at the angle of the rib to innervate the lateral chest, as well as the anterior cutaneous branch supplying the anterior chest wall and upper abdomen [5, 14]. The way the ESPB achieves relief of the bony neuropathic pain at the anterior, lateral, and posterior chest wall suggests that the local anesthetics must target both the dorsal and ventral rami of the thoracic spinal nerve [5, 6]. In other words, the best site of local anesthetic injection should be near the intervertebral foramina where the dorsal and ventral rami split deep (rather than superficial) to the erector spinae muscles [5, 6].

The precise mechanism of action for ESPBs, particularly regarding the pattern and variability of local anesthetic spread to the paravertebral spread, is still under investigation through studies on cadaveric models and in treated patients [6]. In thoracic ESPBs, Yang et al.’s cadaveric study reported consistent distribution of local anesthetics to the paravertebral space [15], whereas Ivanusic et al. found more dorsal ramus involvement but minimal spread of injected agent to the paravertebral space [16]. Other studies found that the extent of local anesthetic spread to the paravertebral space may depend on the level of the block [17] or the volume of injection [18]. Further studies are warranted to better understand the distribution of local anesthetics and improve the efficacy of ESPBs.

The key steps to a successful ESPB are identifying the transverse process and positioning of the needle tip for proper local anesthetic delivery [6]. It is most commonly done at the T5-T7 levels, though lumbar ESPBs have become more widely used in recent years. First, the patient is put in a seated position before a linear ultrasound transducer is placed longitudinally and about 3 cm lateral to the target spinal level. This allows one to obtain a parasagittal view of the trapezius, rhomboid major, and erector spinae muscles superficial to the hyperechoic spinous process [5, 6]. The block needle is then inserted in either a cephalad-to-caudad or caudad-to-cephalad direction until the tip reaches the interfascial layer between the rhombus major and erector spinae muscles, preferably deep to the erector spinae muscles. Upon injection of a bolus of local anesthetic, one should observe a linear separation of fluid between the muscle layers, confirming proper positioning [5, 6, 14]. Typically, 20–30 mL of 0.25% bupivacaine or 0.5% ropivacaine are used. An indwelling catheter may be inserted for continuous infusion or intermittent boluses [5, 14].

2.2 Clinical indications and trials

The ESPB is most commonly used for thoracic procedures. In a systemic review of randomized trials comparing thoracic ESPBs to sham or no block, Saadawi et al. noted that treatment with ESPBs led to reduced postoperative opioid consumptions as well as lower pain scores [6]. These results were reflected in a variety of surgeries, from breast cancer surgery [19] and mastectomy [20] to laparoscopic cholecystectomy [21], splenectomy [22], and open epigastric hernia repair [23]. In a meta-analysis looking specifically at thoracic and breast surgeries, Huang et al. also concluded improvement of postoperative analgesia from ESPBs as well as lower rate of postoperative nausea and vomiting (PONV) compared to no blocks [7]. Furthermore, Huang et al. found that the analgesic efficacy of ESPBs to be comparable to that of thoracic paravertebral blocks (TPVB). The analysis showed no significant overall difference in postoperative pain scores or in incidence of PONV between ESPBs and TPVB [7]. Since it targets a plane further from the pleura and neuraxial structures compared to TPVB, the ESPB may be a promising alternative block with lower risks of pleural puncture and local anesthetic systemic toxicity.

Spinal surgeries have been associated with high postoperative pain scores [24]. Whereas conventional opioid-based analgesia is associated with many opioid-related adverse events (e.g. nausea, vomiting, sedation), the rise of multimodal analgesic—which includes regional anesthesia—allows for improved management of postoperative pain in spinal surgeries. ESPBs. Systemic reviews and meta-analyses have examined randomized controlled trials (RCTs) comparing ESPBs with no block following lumbar spine surgeries, including lumbar decompression surgery, lumbar discectomy, and lumbar internal fixation [12, 13]. These studies have found that patients who had ESPBs in the perioperative period reported lower postoperative pain scores both at rest and with movement for 48 hours after surgery. In addition, ESPB patients consumed less opioids postoperatively, had lower incidence of PONV, and required shorter length of hospital stay. Additional analysis noted further reduction in postoperative opioid use for ESPBs performed at level of incision or operation rather than at fixed level [13]. While the current meta-analyses found that the ESPB provided effective postoperative analgesia in spine surgeries, future studies with higher quality evidence are warranted to confirm the clinical significance and possible superiority of ESP.

While most commonly used in thoracic surgeries, the ESPB also enhances pain management for renal procedures. Adequate analgesia in renal procedures requires the blockade of both somatic and visceral nerves innervating the skin, muscle, kidneys, and ureters. Given that renal pain transmits from the T10 to L1 level, the ESPB offers a promising solution. In a 2019 single-blinded RCT including 50 patients, Ibrahim et al. evaluated the analgesic efficacy of the ESPB compared to no block for percutaneous nephrolithotomy (PCNL) [10]. The block was performed in a single-shot at the T11 level unilaterally. The results showed lower intraoperative fentanyl consumption, lower morphine use 24 h after surgery, and higher rates of patient satisfaction for the treatment group. In addition, Ibrahim et al. noted statistically significant lower pain scale scores at 2 and 12 h in the ESPB group, though with only 1-point lower in pain scores compared to the control which may not be clinically relevant. A RCT study with 60 patients by Abdelgalil et al. compared the ESPB at the T7 level with patient-controlled analgesia (PCA) in open nephrectomy for renal malignancies, showing similar results of lower intraoperative and postoperative opioid consumption for the ESPB group [25]. Furthermore, Abdelgalil et al. found lower pain scores both at rest and with movement in the ESPB group, with a more clinically significant 2-point difference minimum in pain scores with movement in the first 24 h postoperatively compared to the control.

The use of ESPB has been expanded to address pain from the shoulder and upper extremity. A case series by Ma et al. reported successful analgesia with cervical ESPB (performed at the C6 or C7 level) for six patients undergoing shoulder arthroscopy, an intervention for severe rotator cuff injuries typically associated with severe postoperative pain [26]. The study reported that four out of the six patients did not require supplemental postoperative analgesia and that all were able to be discharged home safely the day after surgery. Similarly, a case report by Lee et al. demonstrated the use of ESPB in the emergency department setting for a patient with chronic radicular left arm pain limiting range of motion of the shoulder and elbow despite over-the-counter medications, topical patches, acupuncture, and a variety of other interventions [27]. Lee et al. noted complete relief of pain symptoms and restoration of range of motion for the patient 30 min after receiving the ESPB at the T2 level. The patient also reported complete pain relief for 5 days, with gradual return of symptoms at a more tolerable level afterwards. Together, these preliminary findings presented the ESPB as a potential regional anesthesia technique for upper limb injuries with lower risk of diaphragmatic paresis, upper extremity motor paresis, and nerve injury compared to the more widely used brachial plexus block.

3. Pericapsular nerve group (PENG) block

The pericapsular nerve group (PENG) block is a novel ultrasound-guided regional anesthesia technique that targets the articular branches to the anterior hip joint capsule—namely the femoral nerve (FN) and accessory obturator nerve (AON)—which is the most richly innervated part of the joint [28, 29]. When it was first described by Girón-Arango in 2018, the PENG block was used in perioperative pain management for hip fracture patients undergoing surgical reduction and fixation [28]. The PENG block serves as an alternative to other regional analgesic techniques such as the femoral nerve block (FNB) or fascial iliaca block (FIB) which are popular for hip procedures, with the added advantage of accessory obturator and the obturator nerves block coverage [28].

3.1 Anatomy and technique

Sensory innervation to the anterior hip joint capsule is provided by three nerves: the femoral nerve (FN), obturator nerve (ON), and accessory obturator nerve (AON). The FN, the largest branch of the lumbar plexus, originates from the ventral rami of L2 to L4 nerves and gives rise to the hip articular branches distal to the lateral border of the psoas muscle at around the L5 level which mostly innervate the lateral and superomedial portions of the hip capsule [29]. The ON begins at the ventral rami of the L2 to L4 nerves and passes through the obturator foramen before splitting into anterior and posterior branches at the thigh. The ON articular branches pass through the inferomedial (or “incisura”) of the acetabulum between the pubic and ischial bones to supply the inferomedial area of the hip capsule [29]. Finally, the AON, present in 8–29% of the population [30], originates from the ventral rami of L3 to L4 nerves and descends along the medial border of the psoas major muscle past the superior ramus of the pubis and under the pectineus muscle before splitting into further branches. These AON branches supply the pectineus muscle and join the anterior branches of the ON at the medial aspect of the hip capsule [29].

Past studies have identified FN, ON, and AON as the major nerves of the hip joint, with ON and AON being reported as the most common source of innervation. However, a major cadaveric study in 2017 by Short et al. which included 13 specimens has found consistent innervation of the anterior hip capsule by FNs and ONs specifically, whereas AON branches were found to be less significant contributors [31]. Short et al. also identified pertinent anatomical landmarks for finding the articular branches of the hip joint: the “teardrop” bone thickening of the inferomedial acetabulum for ON, the anterior superior iliac spine (AIIS), and the iliopubic eminence (IPE) for FN and AON [31]. These findings inspired Giron et al. to develop the PENG block in order to more effectively target the FN and AON between the AIIS and IPE [28, 32].

To perform the PENG block, a patient is typically positioned supine with hip extended. For the in-plane technique, a curvilinear ultrasound probe is placed in a transverse plane over the AIIS before rotating 30–45 degrees to align with pubic ramus. This allows one to visualize the iliopsoas muscle and tendon sitting on the IPE along with the femoral artery and the more medial pectineus muscle. Next, a 22-gauge needle may be inserted in a lateral-to-medial in-plane approach to aim the tip in the plane between the psoas tendon anteriorly and the pubic ramus posteriorly. After needle positioning and negative aspiration, a volume of 8–30 mL of local anesthetics (e.g. bupivacaine, ropivacaine, or lidocaine) may be injected for analgesia [28, 32]. With the out-of-plane technique, the ultrasound probe is placed at the level of the anterior superior iliac spine (ASIS) parallel to the inguinal fold then rotated median until the upper pubic ramus is visible. As a result, the target area of local anesthetic injection, i.e. the area between the psoas muscle with a prominent tendon and the pubic ramus, may be located and approached out-of-plane.

3.2 Clinical indications and trials

The PENG block is most commonly used for hip-related analgesia, such as in the setting of hip fractures, pelvic fractures, and hip surgeries. While initial review studies have identified the PENG block as a promising alternative to other regional techniques (e.g. FNB, FIB), most of the evidence was limited to case reports and case series only [33]. In the last 2 years, there has been a rise in randomized controlled studies that strive to examine the safety and efficacy of PENG blocks in order to improve understanding of the novel technique.

When compared against sham placebo blocks or no blocks in total hip arthroplasty (THA), the results on the PENG block were mixed. Pascarella et al. found a significant reduction in opioid consumption, enhanced range of hip motion, and shortened time to ambulation after surgery with PENG block treatment [34], whereas Zheng et al. noted mostly short-term benefits (e.g. reduced intraoperative opioid dosing, lower maximal pain score in recovery room, fewer incidence of PONV) but no notable difference in outcomes upon discharge from recovery (e.g. no difference in pain score or muscle strength) [35]. On the other hand, Amato et al. found no improvement in analgesia for the PENG block treatment group compared to the sham block group after hip arthroscopy [36].

There have been several RTCs comparing the PENG block against FIB in the setting of hip arthroplasty. In terms of postoperative pain level, most RTCs reported little to no difference in pain scores at rest or with movement 48 h after the surgery between the PENG block and FIB groups [37, 38, 39]. Similarly, most studies found no notable difference in the cumulative postoperative opioid consumption or overall length of hospital stay [37, 38, 39]. However, this may vary based on patient condition and demographics. For example, the RCT by Hua et al. specifically examined the analgesic effect of the PENG block in elderly patients (ages 65–85) with femoral neck fracture; they found significantly lower dynamic and static pain scores in the PENG block group, as well as higher patient satisfaction score compared to the FIB group [40].

Several RCTs also looked at the level of postoperative motor function between the two groups [37, 38, 40]. While Choi did not observe differences in quadriceps strength of either the operative or nonoperative legs in the PENG block group versus the FIB group, Aliste et al. found lower incidence of quadriceps motor block (i.e. paresis or paralysis of knee extension) at 3 and 6 h after the procedure in the PENG block group, as well as better hip adduction and thigh sensory function [38]. Similarly, Hua et al.’s study on the elderly population reported quadricep weakness in the FIB group but none from the PENG block group [40]. These results were also reflected in Liang et al.’s study in which the PENG block was combined with lateral femoral cutaneous nerve (LFCN) block. Liang et al. found that the combination of PENG with LFCN blocks led to earlier first postoperative walking time, greater degree of hip flexion, and stronger muscle strength compared to FIB, making the combined block a good candidate for enhanced recovery programs [39]. Overall, the preservation of motor function in PENG blocks offers the advantage of early postoperative ambulation and potentially quicker physical rehabilitation to normal activities.

4. Interspace between the popliteal artery and posterior capsule of the knee (iPACK) block

The interspace between the popliteal artery and posterior capsule of the knee (iPACK) block is an emerging analgesic method for total knee arthroplasties (TKA). First introduced in 2012 by Dr. Sanjay Sinha at St Francis Hospital and Medical Center in Hartford, CT, the iPACK block offers an ultrasound-guided alternative approach to managing posterior knee pain after TKA [41]. Whereas traditional regional anesthetics such as sciatic nerve blocks are associated with delayed functional recovery and motor weakness, the iPACK block aims to provide pain relief while preserving motor function [42].

4.1 Anatomy and technique

The iPACK block specifically targets the distal branches of the sciatic nerve to diminish the occurrence of foot drop, a common complication associated with TKA [43]. At the same time, it addresses pain in the posterior knee region by spreading through the popliteal fossa to the genicular branch of the obturator nerve and the inferior branches of the tibial nerve-nerves that are key analgesic targets for knee surgery [42, 44]. A cadaveric study has demonstrated that injectate consistently surrounds the middle genicular artery and likely involves the articular sensory nerves surrounding the vessel, thereby suggesting a potential mechanism for the iPACK block [44].

The optimal location of iPACK needle site entry remains a subject of ongoing investigation. A RCT showed that a distal iPACK block may result in improved motor function compared to a proximal block above the femoral condyle [45]. The proximal block targets the superior medial and lateral genicular nerves above the femoral condyle, which do not disperse to the sciatic nerve of the popliteal plexus. On the other hand, an iPACK injection below the femoral condyle may spread more effectively to the intercondylar region, thus reaching the popliteal plexus innervating the intra-articular and posterior knee regions [45]. A potential explanation for this difference may be that proximal injections spread more anteromedially, whereas distal injections promote greater anterolateral spread [46]. Further studies are required to confirm the exact mechanism of action.

4.2 Clinical indications and trials

While the iPACK block offers promising results and has been implemented in postoperative care, clinical data remain relatively limited. However, several studies have investigated the safety and efficacy of the technique.

The use of the iPACK block is most commonly combined with adductor canal blocks (ACB) following TKA. Kertkaiatkachorn et al. observed patients receiving either continuous ACB with iPACK treatment versus continuous ACB with periarticular injection (PAI) as an analgesic regimen [47]. The RCT found no significant difference in postoperative pain scores between the two groups. However, the iPACK block group demonstrated an increased IV morphine requirement compared to those in the PAI group. In addition, the iPACK group demonstrated a lower level of immediate ambulatory ability compared to the PAI group, though functional performance recovered with time [47].

Another study by Mou et al. compared three groups of patients receiving ACB and iPACK block, ACB only, and iPACK block only [48]. While patients receiving both ACB and iPACK block reported the lowest pain scores within 8 h postoperatively, those receiving iPACK block only reported the highest pain scores after 12–24 h as well as highest opioid consumption during hospitalization. No significant difference in postoperative complications or function evaluation was observed among the groups. These results suggest that while iPACK may reduce early pain when combined with ACB, the combination may not be clinically significant [48].

A systemic review by D’Souza et al. including eight RCTs (777 patients) assessed whether receiving an iPACK block as an adjunct after TKA would improve patient outcomes [49]. The analysis revealed that the majority of patients who received the adjunct iPACK block experienced no difference in postoperative opioid consumption, level of satisfaction, hospital length of stay, gait distance, and knee range of motion compared to those without iPACK block treatment. Similarly, a meta-analysis of 14 clinical trials (1044 patients) found that an iPACK block with ACB regimen did not improve postoperative pain at 6 hours in the presence of periarticular local infiltration analgesia (LIA) [50]. However, administering an iPACK block as an adjunct to ACB did provide better pain relief when periarticular LIA was not given. Overall, these results suggest that the iPACK block might not add significant clinical benefit as an adjunct.

While the iPACK block was originally intended for use after TKA, clinicians have begun exploring its use after anterior cruciate ligament (ACL) reconstruction. Martin et al. compared the combination of femoral triangle block and iPACK block to local infiltration analgesia after ACL reconstruction [51]. The results showed that even though the iPACK block treatment reduced consumption of morphine 24 h after surgery, it provided no notable difference in outcomes for analgesia or function [51]. This study is one of the few trials that studied iPACK blocks for a non-TKA surgery, suggesting the possibility for the block to be used in ACL reconstruction procedures. A case series has reflected similar results for using iPACK blocks after ACL reconstruction specifically in adolescent patients [52]. The three patients in the study reported minimal pain and no unexpected weakness in dorsiflexion or plantarflexion after receiving only one iPACK block postoperatively. The patients also required very little or no morphine after the procedure; the report confirmed that the iPACK blocks may be safely administered to adolescent patients undergoing ACL reconstruction.

Overall, current literature suggests that while iPACK may offer safe and effective anesthesia for postoperative posterior knee pain, it may not provide meaningful clinical benefits beyond those of standard of care. Although initially meant for use after TKA, the iPACK block may also be useful for ACL reconstruction. Further studies are necessary to better characterize the benefits of iPACK blocks, such as whether to be administered alone or with other analgesic techniques and its efficacy for other types of surgeries.

5. Genicular nerve block and cryoneurolysis for knee

Genicular nerve blocks involve many different branches of nerves from the femoral, saphenous, common fibular, and tibial nerves to innervate the joint capsule. This procedure was first developed to help with chronic knee pain and was later adopted for surgical procedures such as total knee arthroplasty [53]. Genicular nerve block selectively blocks articular branches and is motor-sparing. This can be potentially helpful in early ambulation and faster discharge of the patient following total knee replacement. Genicular nerve block and ablation have also been used as a successful modality in the management of chronic pain from knee osteoarthritis [54].

On the other hand, the use of cryoneurolysis, an opioid-sparing therapy in which cryoprobes freeze peripheral nerves, is becoming increasingly popular [55]. Cryoneurolysis causes nerves to undergo Wallerian degeneration, allowing relief from pain for up to 90 days as nerves regenerate [56, 57]. The device for the procedure utilizes liquid nitrous oxide being converted to a gas, generating a temperature of −125°C [58]. The advantages of cryoneurolysis include increased functional capacity and improved quality of life secondary to pain relief and ability to participate in physical exercise [59].

5.1 Anatomy

The knee is innervated by several different branches around the joint. The various nerves include nerve to vastus medialis (NVM), nerve to vastus lateralis (NVL), nerve to vastus intermedius (NVI), saphenous nerve (SN), common fibular nerve (CFN), recurrent fibular nerve (RFN), superolateral genicular nerve (SLGN), superomedial genicular nerve (SMGN), inferolateral genicular nerve (ILGN), and inferomedial genicular nerve (IMGN) [60]. There is variation in the exact trajectory of the genicular nerves, but the general landmarks around the nerves are fairly consistent across the population. Innervation of the joint capsule can be divided into four main quadrants: superolateral, superomedial, inferolateral, inferomedial.

5.2 Genicular nerve blocks

To perform the genicular nerve block, the patient is placed supine with his or her leg out straight and a pillow placed under the popliteal fossa [53]. Under ultrasound guidance, the articular branches of SMGN, SLGN, and IMGN are identified along the periosteum. There is the option to confirm the correct site for each using a peripheral nerve stimulation needle tip with nerve stimulation [61].

The SMGN starts in the superior popliteal region, tracks around the femur shaft, follows the superior medial genicular artery, then goes between the adductor magnus tendon and the medial epicondyle which is the target location for the block [62]. The superomedial genicular artery should be visible and courses along medially to the SMGN [61]. The SLGN runs laterally along the femur with the superolateral genicular artery and passes between the lateral epicondyle and vastus lateralis. The superolateral genicular artery is found between the vastus lateralis deep fascia and the femur, which is next to the target of the block and lateral to the SLGN [61, 62]. The IMGN lies between the medial tibial condyle and the shaft of the tibia. The inferomedial genicular artery can be seen inferior to the medial collateral ligament and inferomedial to the IMGN target [61]. The ILGN begins in the inferior popliteal region and courses around the tibial lateral epicondyle deep to the lateral collateral ligament, following the inferior lateral genicular artery superior to the fibula head [62]. It lies lateral and distal to the knee in a similar distribution to the RFN. Once each target nerve is identified, a 22-gauge needle can be introduced until bony contact is made with the femur, and 4–5 mL of long-acting local anesthetic (bupivacaine or ropivacaine) may be injected to the area.

The major limiting factor for the genicular nerve block is the fact that the genicular nerve is small while its trajectory is variable. As such, the block is mainly done based on bony landmarks with ultrasound guidance [63]. The option block for the ILGN, which is near the CFN, can lead to inadvertent postoperative foot drop, which may result in an extended time in the hospital waiting for the block to wear off. Due to the proximity to blood vessels and joints, there is an implicit risk of vascular or intra-articular puncture [62, 63].

5.3 Cryoneurolysis

Cryoneurolysis is the application of low temperatures (−20°C to −100°C) to a target percutaneous peripheral nerve to induce Wallerian degeneration; this subsequently disrupts the nerve function while nerve structure remains intact [56, 64]. Since nerve structure remains intact, this allows for complete nerve regeneration and a functional salvage of the nerve over time [65, 66]. Cryoneurolysis provides nonopioid pain relief with a lower risk of infection and no potential for local anesthetic toxicity or catheter dislodgement/leakage commonly seen with other pain management techniques. Additionally, there is a wide margin of safety with cryoanalgesia exceeding traditional local anesthetic-based peripheral nerve blocks, thereby enhancing its clinical utility [67]. The modern cryoprobes utilize gas (usually carbon dioxide or nitrous oxide) to generate extremely low temperatures. The cryoprobes consist of a hollow tube ranging from 1.4 mm to 2 mm with a smaller inner tube that injects pressurized gas at 600–800 psi [68].

Cryoneurolysis can be performed days prior to the proposed surgery. The patient is positioned supine with the leg straightened out and a pillow under the popliteal fossa. The two target nerves are the anterior femoral cutaneous nerve (AFCN) and the infrapatellar branch of the saphenous nerve (IPBSN) [58, 69].

The AFCN courses in the fascia on top of the quadriceps tendon and deep to subcutaneous fat on the anterior aspect of the leg. The target location for AFCN is around 70 mm above the superior pole of the patella [58]. A line in the transverse plane is drawn across the length from the medial and lateral edges of the patella where the needles for the treatment can be placed [58].

The IPBSN runs along the joint capsule and anterior inferior to the head of the tibia. The target location for IPBSN is roughly 50 mm below the inferior pole of the patella just medial to the patellar tendon [58]. A line in the sagittal plane may be drawn across the tibia from the inferior edge of the patella to the tibial tubercle for placement of needles for the treatment [58].

Once the target nerves are located and local anesthetics are applied to the cutaneous tissues, the needles can transmit cooling and warming for around 50 s, starting from one edge of the line to another for six cycles. A series of 2–3 min of freezing with 30 s of defrosting between each cycle is recommended [70]. Patients often note a burning or tingling during treatment which confirms the correct location. The entire procedure takes approximately 15 min [58]. Many newer nerve cryoprobes have built-in nerve stimulators for localization of the nerve and thermistors to detect the temperature, allowing for a wide margin of safety for the devices [70].

There are few relative or absolute contraindications to cryoneurolysis, including anticoagulation, bleeding disorders, localized infection, cryoglobulinemia, cold urticaria, paroxysmal cold haemoglobinuria, and Raynaud’s syndrome [67]. Cryoneurolysis is contraindicated when extremity muscle demonstrates extreme weakness, such as ablating the femoral nerve for analgesia following a knee surgery in which the weakened quadriceps muscle prevents postoperative ambulation [67]. Other risks include bleeding, bruising, and minimal damage to surrounding tissue as the tissue may adhere to the frozen probe [58, 68]. After the procedure, there may also be depigmentation or hyperpigmentation [68].

5.4 Comparison to other knee blocks and future research

There is a limited number of studies that directly compare the genicular nerve block or cryoneurolysis. However, one study demonstrated that interspace between the popliteal artery and capsule of the knee (iPACK) block and the genicular nerve block both significantly reduced postoperative pain with no difference in time to mobilization after surgery. In fact, the genicular block was found to provide better pain relief 4 and 8 hours postoperatively when the patient is ambulating [71]. A recent review article found no RCTs for genicular nerve blocks to date, despite preliminary studies demonstrating for postoperative pain [72].

New techniques and devices for cryoneurolysis are being tested that utilize local injection of a “cold slurry” containing normal saline with 15% glycerol from −5°C down to −9°C. This can minimize the limitations of the current cryoneurolysis devices [55]. There is also ongoing research to optimize probe design [73]. Development of newer types of local anesthetics may also impact the future of genicular blocks.

Total knee replacement is a major surgery associated with significant postoperative pain. Therefore, nerve blocks are often used prior to the surgery to alleviate pain and potentially reduce opioid use. Additionally, cryoneurolysis may also provide longer pain relief than standard knee blocks. The techniques for these two procedures are fairly easy and mostly landmarked-based rather than requiring direct visualization. Further research into the safety and efficacy of the two procedures will allow for better assessment and understanding of appropriate clinical application for patients.

6. External oblique intercostal block

The external oblique intercostal (EOI) block is a novel superficial plane regional anesthesia technique that offers promising benefits for postoperative analgesia in upper abdominal surgeries [74]. The external oblique muscle is the most superficial muscular layer of the abdominal wall. Covering the anterior and lateral parts of the abdomen, it attaches to the lower eight ribs and runs inferiorly, medially, and anteriorly, ending midline at the linea alba [75]. It is innervated by the motor branches of the lateral cutaneous branches of anterior spinal nerves from T5 to T12 [76]. A limited cadaveric study revealed that dye injections to the site of EOI blocks effectively spread to both the anterior and lateral cutaneous branches of the T6/T7 to T10/T11 intercostal nerves; this distribution may explain the mechanism of EOI injection [75].

In patients, EOI blocks are performed with subjects lying supine; the sixth and tenth ribs are identified by ultrasound. The injection entry point is at the level of the sixth rib medial to the anterior axillary line. The needle is advanced in a superomedial-to-inferolateral direction, through the external oblique muscle, until the tip lies between the external oblique and intercostal muscles at the caudal end of the rib [75]. With the EOI block, patients should experience consistent sensory blockade of T6 to T9 at the midline and T6 to T10 at the anterior axillary line [75]. This technique has been shown to be effective in bariatric and liver surgery with patients having reduced opioid consumption and improved postoperative pain scores [77, 78, 79].

Obesity is associated with higher rates of complications and block failure. One challenge includes technical difficulties related to the depth of the target site [80, 81]. Obesity is an important consideration in regional anesthesia and often considered a contraindication for procedures such as paravertebral blockade, thoracic epidural analgesia, and erector spinae plane catheter insertion [81]. A case study reported successful administration of EOI block in two morbidly obese patients despite technical challenges [81]. This suggests the potential for EOI blocks to be used in a wider patient population compared to other regional analgesic methods. Future studies should further investigate the efficacy of EOI blocks in larger cohorts of obese patients in order to better understand the benefits, potential complications, and long-term outcomes of EOI blocks in this specific population.

In addition to its potential use for a wider patient population, the EOI block presents several advantages over other alternatives. For example, the transabdominal plane (TAP) blocks inconsistently block the innervation to the upper abdominal wall. Depending on the approach, subcostal TAP blocks typically cover either T6 to T7 or T10 to T11, but not both simultaneously [75]. In addition, unlike EOI blocks, TAP blocks often fail to block lateral cutaneous branches, thus limiting use in several abdominal surgical procedures [75, 82]. In contrast, EOI blocks seem to provide more for upper abdominal surgeries, though further research is needed to establish its efficacy, safety, and optimal application.

7. Long-acting local anesthetics and block adjuncts

Long-acting local anesthetics may be explored as potential solutions to improve analgesia and reduce postoperative opioids use. Traditional local anesthetics, such as lidocaine and bupivacaine, provide short- to intermediate-term pain relief. However, their duration of action is limited, leaving patients in pain once the effects subside and thus requiring other medications such as opioids for pain control.

Current research has focused on formulating new local anesthetics with liposomal or lipid-based delivery systems. The aim is to prolong the duration of analgesia, thereby reducing the need for additional pain interventions. These systems encapsulate the anesthetic drug, allowing for slow and sustained release over an extended period. By controlling the release rate, these formulations can provide analgesia for several days, significantly reducing the need for opioids postoperatively. Another strategy involves using novel compounds or modifying existing local anesthetics to enhance the duration of action. These modifications include adding additives in nerve blocks or altering the chemical structure of the drug to increase potency or delay metabolism, thereby extending the analgesic effects. Preliminary studies and clinical trials have shown promising results with some of these long-acting local anesthetics.

7.1 Liposomal bupivacaine

Liposomal bupivacaine, also known as extended-release bupivacaine, is similar to a micelle, creating a bilayer of lipids with bupivacaine inside the structure. In 2011, Bupivacaine liposome injectable suspension (Exparel) was approved as a local anesthetic by the US Food and Drug Administration (FDA) for single-dose infiltration in adults for postsurgical local anesthesia and for interscalene brachial plexus nerve blocks [83, 84]. The drug has a slower release than typical bupivacaine due to its liposomal structure which substantially prolongs the analgesic effects [85].

When liposomal bupivacaine is administered, the local anesthetic effect diminishes over time while the systemic levels of bupivacaine may persist for up to 96 h [86]. The prolonged effect makes liposomal bupivacaine beneficial for postoperative analgesia. To prevent unintentional overdose and systemic toxicity, one should avoid administering immediate-release bupivacaine or other local anesthetics for at least 96 h after liposomal bupivacaine use [86].

The evidence supporting the effectiveness of liposomal bupivacaine for postoperative pain management has been limited. A review by Ilfeld et al. looked at 12 placebo-controlled RCTs investigating liposomal bupivacaine infiltration into the surgical site for postoperative pain management after procedures in the trunk, extremities, and dentition [87]. Only five of the 12 RCTs demonstrated improved pain management from liposomal bupivacaine compared to the placebo control group [87]. Furthermore, Ilfeld et al. noted an increased risk of bias in all five RTCs [87, 88, 89]. When comparing liposomal bupivacaine to traditional bupivacaine hydrochloride, an older and shorter-acting analgesic, only two out of 19 RTCs reported statistically and clinically significant difference in postoperative pain scores for liposomal bupivacaine after various surgeries (excluding knee arthroplasty). Similarly, only two out of 17 RCTs for knee arthroplasty found a significant difference in pain scores and postoperative opioid use for the liposomal bupivacaine group compared to traditional bupivacaine [85, 87, 90, 91].

RTCs evaluating single-shot nerve blocks and continuous peripheral nerve blocks for knee and shoulder procedures found liposomal bupivacaine to be superior to typical anesthetics for pain control and reduced postoperative opioid consumption [87, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102]. However, RTCs on liposomal bupivacaine use in TAP blocks and epidural blocks after abdominal surgery showed mixed results; there was no difference in pain scores or postoperative opioid use between TAP block using liposomal bupivacaine compared to epidural blocks with fentanyl [103].

7.2 Bupivacaine/meloxicam

Bupivacaine/meloxicam (Zynrelef) is a combination drug in fixed doses of the local anesthetic, bupivacaine, and meloxicam. This is a prolonged-release formulation that lasts approximately 72 h and is applied with a needle-free technique into a surgical site where it can target local tissues just below the skin. Phase III clinical trials using bupivacaine/meloxicam in bunionectomies, herniorrhaphies, and total knee arthroplasty have demonstrated a statistically significant decrease in pain and opioid consumption compared to placebo and bupivacaine hydrochloride. Wound healing was not impacted, and adverse effects were similar to placebo [104].

7.3 Lidocaine infusion

The proposed benefits of continuous systemic lidocaine infusion in the perioperative setting is to reduce the need for opioids and inhaled anesthetic agents as well as allow for the return of bowel function after surgery to shorten the length of stay in the hospital [105]. A systematic review of 68 trials included studies that compared lidocaine infusion to thoracic epidural analgesia, placebo, or no treatment during general anesthesia cases that were either urgent or elective. The procedures studied included open abdominal and laparoscopic abdominal surgeries. Lidocaine infusion was started prior to the incision intraoperatively and continued until at least the end of the surgery. There was no clear evidence of improvement in pain scores, return of bowel function after surgery, or lower opioid consumption compared to placebo or no treatment. In addition, there was insufficient evidence for lidocaine infusion compared to epidural anesthesia since the studies varied in dosing and timing of the infusion [106].

7.4 Mepivacaine

Mepivacaine is an intermediate-acting local anesthetic with a shorter duration at around 1.5–2 h. Review articles of RCTs and retrospective cohort studies have compared mepivacaine and bupivacaine for spinal anesthesia in total hip arthroplasty and total knee arthroplasty [107, 108]. The results found that mepivacaine treatment is associated with higher incidence of complete motor blocks, shorter hospital stay, faster resolution of the motor block, sooner return to normal voiding function, and earlier time to ambulation compared to bupivacaine. However, mepivacaine also had higher incidences of transient neurologic symptoms and transient nerve root irritation than bupivacaine. There was no significant difference in pain scores or distance walked after surgery despite early ambulation with mepivacaine [107, 108].

In a meta-analysis that includes seven RTCs with 672 patients, Fu et al. compared mepivacaine and bupivacaine in combination blocks for the femoral and sciatic nerves, interscalene brachial plexus blocks, and spinal anesthesia [109]. Their findings showed that patients receiving mepivacaine experienced significantly faster return of motor function and shorter length of hospital stay. However, mepivacaine use was also associated with increased postoperative analgesic requirements such as opioids and nonsteroidal anti-inflammatory drugs (NSAIDs). This could be due to the shorter duration of action of mepivacaine, as well as early ambulation with mepivacaine leading to more pain from movement. Finally, no difference was found in postoperative pain scores, complications from blocks, or patient satisfaction between mepivacaine and bupivacaine [109].

7.5 Prilocaine

Prilocaine, a local anesthetic, has an intermediate length of duration with a fast onset of action. It is cleared faster than lidocaine and less likely to reach toxic blood levels, thus contributing to minimal side effects [110]. Prilocaine has been found to be particularly useful for spinal anesthesia in low doses [111]. Compared to bupivacaine, prilocaine use in obstetric anesthesia for cesarean sections was associated with a significantly reduced duration of the motor block and subsequently shorter stay in the post-anesthesia care unit [112]. Recently, 2% hyperbaric prilocaine has been approved for intrathecal use in Europe for 60- to 90-min procedures; however, it is only available for dental procedures in the US. While lidocaine may cause transient neurologic symptoms as a side effect in 10–40% of patients, intrathecal prilocaine may be a better option due to its lower incidence [111].

7.6 QX-OH/levobupivacaine (LL-1)

QX-OH is a quaternary lidocaine derivative shown to maintain local anesthetic effect over a long period in rats [113]. When QX-OH is combined with levobupivacaine (QX-OH/Levo-Bupi, or LL-1), the constant concentration ratio of 35 mM/10 mM was found to achieve the longest duration of action while having moderate local toxicity (QX-OH/Levo-Bupi, denoted as LL-1) [114]. This new combination in fixed-dose has shown good efficacy and fast onset of analgesia in animal models. Studies have shown that the two drugs create an additive effect of inhibition of sodium currents across cell membranes. In addition, LL-1 offers the advantage of low tissue toxicity in local injections [115, 116, 117]. Further investigation of LL-1 in human subjects is warranted.

7.7 Hydrogel/microsphere composite of bupivacaine and dexmedetomidine

A hydrogel/microsphere composite co-delivers local anesthetic bupivacaine in the microsphere and alpha-2 (a₂)-adrenergic receptor agonist dexmedetomidine in the hydrogel matrix; it was developed to prolong analgesia in single injections [118]. The goal was to release dexmedetomidine from the hydrogel and constrict surrounding local arteries to reduce bupivacaine uptake, similar to the role of epinephrine when combined with lidocaine for local anesthesia. Bupivacaine is released over a longer period to lengthen the duration of analgesia. Rat model studies of this extended-release drug formulation in sciatic nerve blocks have demonstrated a longer duration of nerve block while minimizing systemic toxicity from bupivacaine. This drug delivery system offers a viable strategy to extend the duration of single-shot nerve blocks for surgery [118].

7.8 Injectable electrospun fiber-hydrogel composite

An injectable regional anesthetic composite combining Rop-loaded electrospun nanofiber and Clo-loaded F127 hydrogel is a single-shot composite drug made of a poly-electrospun fiber of ε-caprolactone loaded with ropivacaine and F127 hydrogel loaded with clonidine [119]. Clonidine is released from the hydrogel to constrict neighboring local arteries while reducing ropivacaine uptake. Then, ropivacaine is slowly released over time to prolong blockage to the target area. Testing of the drug on rat models for sciatic nerve blocks showed the sensory and motor blocks lasting around 32 h and 20 h, respectively. This means a significant time with minimal pain and intact motor function. The injectable electrospun fiber-hydrogel composite may be useful for total knee arthroplasty and total hip arthroplasty [119].

7.9 Dexmedetomidine

Dexmedetomidine is a selective α₂-adrenoreceptor agonist which provides sedative, analgesic and anxiolytic properties. Clonidine, another adjunct which works on the same receptor, is eight times less specific for α₂-adrenoreceptor compared to dexmedetomidine [120]. The α₂-adrenoreceptor is a G-coupled protein widely found in the periphery, central nervous system and autonomic ganglion. When acting on the locus coeruleus nucleus, dexmedetomidine provides sedative and hypnotic effects. At the dorsal horn, it reduces the secretion of pain transmission molecules such as substance P and glutamate [121]. Dexmedetomidine also maintains the hyperpolarization state of interneurons by inhibiting I_h current. This leads to an amplified anesthetic effect on unmyelinated C pain fibers and small myelinated A-δ fibers which detect temperature and rapid pain sensation. In contrast, large myelinated motor fibers are less affected [122]. At lower doses, dexmedetomidine decreases heart rate and blood pressure by reducing vascular resistance. At larger and rapid doses, it is no longer selective, thereby causing increased blood pressure and decreased heart rate. Combining dexmedetomidine with local anesthetics in peripheral nerve blocks has demonstrated stronger analgesic effect and prolonged duration by 4–5 h compared to using local anesthetics alone [123]. This can be attributed to the drug’s effect throughout the spinal cord, its ability to inhibit δ and C fibers and the vasoconstrictive properties leading to reduced absorption of local anesthetics [124]. In a meta-analysis looking at perineural dexmedetomidine in brachial plexus blocks, dexmedetomidine provided an increase in mean analgesia duration by 4.5 h–specifically 4 h of sensory block and 3 h of motor block. It also decreased the mean time onset for these blocks by 8–9 min. The optimal dose of perineural dexmedetomidine providing the longest sensory blockade with minimal adverse effects is 50–60 mcg [125]. Some adverse effects of dexmedetomidine to keep in mind are bradycardia, hypotension, and excessive sedation.

7.10 Intravascular and perineural dexamethasone

Dexamethasone is a long-acting glucocorticoid with minimal mineralocorticoid activity. It works as an anti-inflammatory by inhibiting cyclooxygenase-2 and prostaglandins. When administered perineurally, it is thought to increase inhibitory potassium channels, leading to decreased excitability and neuronal transmission in nociceptive unmyelinated C fibers responsible for pain [120]. Dexamethasone can be administered intravenously or perineurally to reduce postoperative pain and opioid consumption. Both routes as adjuncts have shown to prolong analgesia duration by approximately 6 h compared to the control group with no adjunct [125, 126]. In an meta-analysis testing the efficacy of perineural versus intravenous in brachial plexus blocks, the perineural route prolonged the duration of analgesia, sensory block, and motor block by approximately 132 min, 210 min, and 219 min respectively compared to intravenous dexamethasone [127]. Although perineural administration led to prolonged duration of action, many still recommend using IV dexamethasone at 0.1–0.2 mg/kg in patients undergoing moderate or severe surgeries because of its lower rates of PONV [128, 129, 130]. Discussion about the optimal dose for dexamethasone is still ongoing; some studies showed that perineural dexamethasone at high doses have no advantage but carry increased risk compared to lower doses. A randomized trial comparing 2, 5 and 8 mg perineural dexamethasone in infraclavicular blocks found similar durations of sensorimotor block [131]. Therefore, higher doses of perineural dexamethasone are no longer recommended. More studies to investigate the most effective dose for perineural dexamethasone are necessary.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.