Regional Anesthesia Roundtable: An International Expert Panel

Anesthesiology News

Once again, Kamen V. Vlassakov, MD, the director of the Division of Regional and Orthopedic Anesthesia at Brigham and Women’s Hospital in Boston, assembled an international expert panel of regionalists and asked them to respond to 7 questions that the group created. Herewith, 7 questions for 7 anesthesiologists…

1.What do you consider are the best measures of success for our regional anesthesia and acute pain medicine (RAAPM) procedures and strategies? Is it time to reevaluate our goals?

Dr Barrington: Best measures of success for our RAAPM procedures are patient-reported outcomes. Here are 2 examples:

• The 15-item validated Quality of Recovery score (QoR-15) can be applied in the postoperative period. The questions comprise 5 domains of testing: pain (2 questions), physical comfort (5 questions), physical independence (2 questions), psychological support (2 questions), and emotional state (4 questions). Each question uses an 11-point scale ranging from 0=none of the time to 10=all of the time (scoring is reversed for negative questions). The sum of the individual domains generates an aggregate score with the maximum score (best recovery) obtained being 150. For moderate-impact surgery, an average QoR-15 score of 118±20 would be expected. The QoR-15 score can be collected before or on the day of surgery and again at 24 to 48 hours post-surgery.
• The Brief Pain Inventory (short form) is a widely used questionnaire that assesses pain and its interference with physical and emotional functioning. There are three domains: 1) pain (4 questions) assessing worst, average, least, and current pain levels using an 11-point numeric rating scale; 2) percentage of relief provided with pain treatments (1 question); and 3) interference with physical and emotional functioning (7 questions using an 11-point Likert scale [0, no interference; 10, complete interference]). The composite score ranges from 0, optimal, to 120, worst possible. The Brief Pain Inventory can be administered preoperatively and in the postoperative period, for example, on postoperative days 1 to 3 and at 3 months postoperatively to assess persistent postsurgical pain and long-term opioid usage.

Dr Gabriel: I do not think there is any one “best measure” for RAAPM. It is a balance between effective analgesia, minimization of side effects/complications, patient satisfaction, service satisfaction (ie, the surgical team, anesthesia), operating room (OR) efficiency, and costs (whether it is cost-saving or profitable). I think it is important to keep all of these things in mind when defining the success of a regional anesthesia or acute pain service. When defining the success of the block itself, this has to do with whether the block was sufficient to provide surgical anesthesia (if that was one of the purposes) and significant opioid-sparing analgesia. Oftentimes, we see these patients receive minimal intraoperative anesthesia and then are discharged home in less than an hour without taking any opioids, even after something like an open reduction, internal fixation radius fracture or a bunionectomy. Furthermore, if they have an ambulatory catheter, they are provided with opioid-sparing analgesia for the next 3 days! Seeing this, to me, means the block was completely successful. It is, however, important to weigh this with the other major points discussed earlier.

Dr Horn: Our success in the area of RAAPM is validated by our surgical colleagues and administrators, through benchmarking time efficiency. In addition, surgeons appreciate good blocks with impeccable follow-up. Without time efficiency and quality work, the practice will vanish. Our vision to achieve success includes the creation of a multisystem process. It starts with the preoperative identification of patients to schedule early arrival and inclusion in a protocolized pathway to ensure zero delay.

Education of all parties, including administrators, technicians, pharmacists, surgeons, colleague anesthesiologists, nurses, and patients promotes the successful implementation of the process. Follow-up starts in the preoperative area, where a successful block must be declared before surgery, and reassessed in the PACU before discharge and then daily assessment of catheters, whether inpatient or ambulatory. Long-term follow-up includes management of block-related complications and persistent/transitional pain. Rebound pain after regional anesthesia is a consideration to be aware of and ready to assess and manage. A personal pearl: When a catheter is placed for postoperative pain, I do not inject any local anesthetics through the needle in order to ensure the functionality of the catheter.

Dr Le-Wendling: I believe the goal of any optimal analgesic intervention is to maximize functional recovery (with daily activities and rehabilitation) for the best pain relief. This does require an effective regional technique that minimizes dependence on opioid consumption and a reduction in rebound pain. An effective regional anesthetic should be tested constantly, such as immediately after placement, immediately postoperatively in the recovery area, and twice a day thereafter. Effective therapy (type of intervention and its duration) must be chosen to match the patient’s pain trajectory. Checking for accurate continuous catheter placement should include documenting the rate of secondary failures.

Dr Lobo: Success can be very difficult to define. It really depends on meeting the goals and expectations of everyone involved: anesthesiologist, surgeon, and most importantly, patient. You can have a perfect block and a very unsatisfied surgeon/patient, and the other way around. It would be important to have a definition and criteria of success that could be applied generally to regional anesthesia techniques, making it easier to study and compare techniques and acute pain protocols. But what is success for me? It can be many things. For example, a high success rate, a low complication rate, placing a properly performed block for the right patient, using a technique that suits the surgeon, adjusted intra- and postoperative pain management, reduced complication rates and lowered opioid needs, and a positive impact on mortality and morbidity rates. Most important for me is that the regional anesthesia technique has a helpful influence on the patient’s surgery and/or recovery.

In my everyday practice, I try (mainly and if possible) to consider the patient’s expectations, keeping safety as a main goal. Sometimes the perfect block does not suit a particular patient, as he might prefer a less perfect block and keep some sensory and motor function. There must be a compromise between parties in finding the best for all, even if it sounds like an impossible mission. Postoperative follow-up is of utmost importance to make proper analgesia adjustments and promptly detect complications.

Dr Ludwin: Patient satisfaction is one of the most important metrics of success for our RAAPM procedures and strategies. Perioperative education and management of expectations are essential for optimizing patient care. Patients and health care providers need to have a clear understanding of what RAAPM can provide and what the limitations are. The onus is on us as anesthesiologists to make sure we evaluate our own practices and ensure that we contribute to the education and teaching of our patients and other health care providers.

To assess the quality of our nerve blockade, we can perform sensory and motor testing. Using databases, we can track our success rates looking at percentages of regional procedures for surgical anesthesia that require an unexpected conversion to general anesthesia.

We often look at the success of our blocks in the immediate perioperative period, including the OR and the PACU. Data collection from postoperative time points further out, such as postoperative day 1, day 2, week 1, month 1, and months 3 and greater would give us a better sense whether our current practices affect outcomes longitudinally.

Dr Vlassakov: Our collective passion and hard work in regional anesthesia has always focused on providing the best short-term and long-term benefits for our patients, as per our current understanding. Still, we have yet to achieve an optimal understanding of pain trajectories after surgery and trauma, and a true consensus on the best ways to evaluate, follow, and record block success, including such seemingly basic premises as standard time points for evaluation (eg, PACU admission, PACU discharge, 1 day postoperatively).

Yes, we need to reevaluate our immediate comprehensive goals as regionalists and as multispecialty teams—accelerated and complete functional recovery being the new prioritized focus—and pain (scores) and opioid sparing are among our main measures (not goals) to achieve that. Persistent pain, cancer recurrence, preventive analgesia, and other important longer-term outcomes should continue to play an increasingly important role in (re)defining our multidisciplinary strategies.

Tailoring perioperative analgesia not solely to a traumatic injury or surgical procedure but to our patient’s individual psychosocial, neurophysiologic/neuroanatomic, and pharmacogenetic profile should be our next challenge and masterpiece! But first, we need to define clear, scientifically validated, and clinically justified measures of success; educate ourselves, then our patients, surgeons, and coworkers; and systematically follow up, analyze, benchmark, adjust, adapt, and improve our practices. And frankly, if we do not do this ourselves soon and well, someone else will do it for us.

2.Opioid-free analgesia—is this a realistic and/or worthy goal, and how would it best be achieved? What about neuromodulation and cryoanalgesia for acute and postoperative pain management?

Dr Barrington: I have not mastered opioid-free analgesia yet. Clearly, given the current opioid epidemic, we need to focus our efforts on how to minimize exposure to perioperative opioids. I am open to any local anesthetic or nonpharmacologic therapy that will achieve this goal. Patient and health care professional education is important for achieving opioid-free analgesia. What I observe repeatedly is the expectation that opioids will always (except for the most minor of surgeries) be written onto the postoperative medication chart. I observe the routine use of opioids to manage perioperative pain, often with no overt consideration on how this exposure can be mitigated. The patient-reported numeric rating scale for pain is often used as the baseline and opioids are titrated to effect so as to treat and reduce this number, often irrespective of other considerations, including opioid tolerance, opioid-induced hyperalgesia, and longer-term risks such as opioid abuse and misuse.

Dr Gabriel: For some patients (depending on the surgery and patient comorbidities), it is possible to achieve opioid-free analgesia; however, this is only a select group. I’ve seen many patients get the same surgery, have the same comorbidities, have the same multimodal analgesia plan, and have the same regional blockade, but one would still use more opioids than another. There is an inherent difference between patients, whether it’s a component of psychosocial makeup or pharmacogenomics, that we do not fully understand quite yet. Once we master not only the multimodal analgesia plan but also these other understudied components, we can get better at providing opioid-free analgesia. By contrast, opioid-sparing (rather than opioid-free) multimodal analgesia pathways are very possible today. This will require interdisciplinary collaboration, especially between an expert pain team/consultant and the surgical services. The concept needs to be both evidence-based and practical. Institutions should hire experts when they are lacking. We also have to remember that opioid sparing should continue after the acute period, oftentimes when anesthesiologists are no longer involved. This is why it is important to get surgeon buy-in and have excellent collaboration between the pain consultants and the primary service.

At our institution, we are actively studying the use of ultrasound-guided percutaneous cryoanalgesia and peripheral neuromodulation for acute pain. Both modalities are being studied in multicenter randomized controlled trials. These are novel modalities that may potentially be used to provide weeks to months of analgesia (compared with the few days with local anesthesia continuous nerve blocks). More to come!

Dr Horn: Opioid-free anesthesia is realistic, with good regional anesthesia, but the real question remains: Is opioid-free anesthesia realistic for major surgery with no regional? I believe it is, although I prefer to focus on the concept of opioid-sparing anesthesia. Using that strategy, analgesia is achieved with advanced multimodal analgesia including alpha-2 agonists, ketamine, lidocaine infusions (although I am not convinced of its utility outside of abdominal surgery), and other nonopioid medications. When opioids seem indicated, I prefer to use methadone to provide NMDA (N-methyl-D-aspartate) blockade with long-duration opioid analgesia.

Neuromodulation will be a key modality for acute pain management once its application is better defined and its cost reduced. It can potentiate local anesthetic action and may replace local anesthetics. Cryoanalgesia seems very attractive but should be considered carefully and reserved for experts, given the risk for permanent nerve injury when improperly applied to a motor or sensory neuron.

Dr Le-Wendling: This can be a realistic goal for a subset of individuals, given that the public perception of opioids in North America may be changing. More so than ever, patients are requesting opioid-free anesthesia. The success of opioid-free analgesia hinges on the patient’s expectations, less traumatic surgical technique, and an in-depth understanding of the pain trajectory. More importantly, the duration of analgesia has to match the trajectory of moderate to significant postoperative pain. Sadly, every intervention, whether pharmacologic or procedural, will carry with it a certain risk profile. Complete avoidance of opioids probably should not be our goal, but rather sparing of opioids.

At this time, neuromodulation is not ready for implementation due to limitations with equipment and cost. However, the ability to provide analgesia without the side effects and complications (motor effects, systemic toxicity) from using local anesthetics is very appealing. Cryoanalgesia also sounds promising, but the inability to tightly control its duration of effect (such as loss of motor function) is unappealing.

Dr Lobo: Opioids are fantastic drugs when used properly; as Paracelsus said, “The dose makes the poison.” They are still the main analgesics for intra- and postoperative periods. When physicians inform patients about the side effects of opioids, the risk for addiction should be included. The risk for addiction exists even for low-pain surgeries.

Its uncontrolled prescription in the United States has led to an opioid epidemic that, for the time being, has no parallel in Europe. This fact raised concerns and was a red flag that started a search for “novel” analgesic methods (eg, regional and multimodal analgesia, alpha-2 agonists) in order to reduce or avoid opioid use. There is also the fact that opioids decrease immunity and thus jeopardize a patient’s recovery. So I think this is realistic and a goal worth pursuing. But this goal should not compromise being a pain-free patient.

The best way to achieve an opioid-free analgesia (I prefer the expression reduced-opioidanalgesia) is through education of patients and the medical community on different ways to manage pain—for example, regional analgesia, adjuvants, peripheral nerve catheters, ketamine, alpha-2 agonists.

Dr Ludwin: The opioid crisis has led us to reconsider the role of opioids in the perioperative period and to minimize patients’ risk for addiction and dependence. Adequate pain control is imperative for patient satisfaction as well as functional recovery. At our institution, we still incorporate the option of opioid analgesia. However, we have shifted our practice toward aggressive multimodal analgesia with a significant reduction in opioid use.

Dr Vlassakov: In my opinion, opioid-free analgesia is both possible and worth pursuing, but as with everything else, it should not be turned into a dogma. It seems unrealistic and impractical (and even wrong!) to eliminate opioids from our armamentarium. We should start with opioid sparing, then go to opioid backup only, and then aim for opioid-free when possible. Multimodal nonopioid analgesia, anchored around optimized and aggressive regional anesthesia, can go very far in perioperative pain management. Novel applications of alternative analgesia concepts, such as neuromodulation and cryoanalgesia, may also prove valuable in the perioperative setting. Changing the culture in health care, including patient expectations, but also getting buy-in from all health care providers, from anesthesiologists and surgeons to nurses, families, and primary care physicians, remains pivotal.

And if I may challenge (and even provoke) our readership, could we start this tomorrow by minimizing and even eliminating opioids from our premedication?! Do we really need to give fentanyl (or the like) before virtually every peripheral nerve block, or could we simply go with the proverbial TLC, better local infiltration, and optional light anxiolytics only, in addition to the other widely used nonopioid multimodal medications?

3.How have you and your hospital been dealing with the present shortage of various opioids and local anesthetics?

Dr Barrington: In our hospital, the most significant shortage has been for epinephrine-containing local anesthetics. There is sufficient quantity of the remainder of local anesthetics, and we can add epinephrine to the injectate if required.

Dr Gabriel: We have developed various committees and clinical services that address this very issue. Both our acute pain service and regional anesthesia service are led and run by regional anesthesia–trained anesthesiologists. We developed and adapted various pathways that address these issues in order to maintain success in our services. Furthermore, we have collaborated with our surgical colleagues and pharmacists to develop pathways that spare opioids.

Dr Horn: Our hospital pharmacy is keeping us updated on stock levels of each opioid and we always have sufficient opioids available. I would have cancelled elective surgery if I had been concerned regarding patient safety or improper postoperative pain care. Fortunately, I did not have to cancel a single case, to my surgeons’ great satisfaction. In fact, the opioid epidemic and shortage have forced me to reevaluate my practice in the area of pain management and review alternative modalities. I started using vitamin C and magnesium routinely; I administer ketamine to most of my patients; and for painful cases, I use methadone.

Dr Le-Wendling: With the opioid shortage, we restrict opioid use for procedural interventions only to patients with significant central sensitization, pain from positioning in trauma patients, and trauma patients where we are unable to solely use ultrasound-guided regional anesthesia and need nerve stimulation. No patient-controlled analgesics (morphine, hydromorphone) have been prescribed in our institution, unless for cancer pain or significant trauma. We have increased our use of ketamine as a substitute for opioids. We have explained preoperatively to our patients on chronic high-dose opioids the lack of available IV opioids to allow rescheduling of elective procedures. With regard to local anesthetic shortages, we have begun using ropivacaine 0.2% more frequently for bolus dosing, and find that we still can achieve surgical anesthesia. For continuous infusions, our pharmacy has been reconstituting infusion bags for home use from ropivacaine vials/bottles.

Dr Lobo: In Portugal, we haven’t faced any important shortage of opioids and local anesthetics currently. A few years back, the ampule of lidocaine and epinephrine was removed from the market. So, whenever necessary, we had to mix ourselves. Otherwise, any shortage is normally short-lived, for example, a stock shortage that is resolved in a couple of days.

As far as use of opioids for chronic pain, there have been some difficulties in finding hydromorphone 4 mg and transmucosal fentanyl 600 mcg for public and hospital pharmacies. In such cases, we replace them with other drugs (morphine, buprenorphine, for example).

Dr Ludwin: We have tried to be as proactive as possible. For example, as bupivacaine became limited in supply, we worked together with our pharmacy so that the pharmacists would aliquot bupivacaine sterilely for spinal anesthesia, and we were able to greatly decrease waste. For peripheral nerve blocks, we use saline for hydrolocalization. This allows us to be more efficient with our use of local anesthesia instead of wasting some local anesthetic to identify correct fascial planes.

Dr Vlassakov: These fluctuating shortages have presented significant logistical and sometimes therapeutic challenges, but they have also created opportunities. On one hand, our role as anesthesiologists and perioperative physicians in the relevant hospital committees has become more visible and appreciated. On the other hand, all concerned specialties have been forced out of old routines and comfort zones into better collaboration, wherein we reevaluate our practices and innovate together. Inadvertently, the prolonged and wide-ranging opioid shortages arguably may have brought about more significant inpatient opioid use reduction than any other planned and debated measure. The shortages of bupivacaine are not as disruptive but might also direct us toward using local anesthetics with lower potential toxicity and at lower, yet effective, concentrations.

4.Do you use local anesthetic “extenders” in your blocks, such as dexamethasone, dexmedetomidine, and epinephrine? What is your rationale and your experience with such additives?

Dr Barrington: I often use dexamethasone, dexmedetomidine (or clonidine), epinephrine, and buprenorphine. I acknowledge that the evidence for some of these additives is evolving. Anecdotally, I can report good results for clonidine (75-100 mcg), buprenorphine (100-150 mcg), and dexamethasone (2 mg) for prolonging the duration of effect of distal femoral triangle blocks following total knee replacements. If prolonged analgesia is required, then my bias is to use a continuous catheter technique. I have no experience with liposomal bupivacaine (Exparel, Pacira).

Dr Gabriel: We routinely use ambulatory catheters for continuous nerve blocks and very rarely use additives. In the event where a catheter is not used but it is felt that a prolonged block would be required, we tend to use either clonidine or dexamethasone. Our experience has been that they indeed prolong the block and are useful, especially in places that do not routinely place catheters.

Dr Horn: I do not routinely use extenders, as none, except for epinephrine, are FDA approved, and we have an efficient catheter practice. When a catheter is contraindicated and a single injection is not sufficient, I administer a combination of alpha-2 agonist, buprenorphine, and low-dose dexamethasone to achieve a 24- to 48-hour block. I have stayed away from adding epinephrine due to its potential for neurotoxicity/ischemic injury to the nerve. I also like to minimize steps to avoid errors and contamination, although it may be just laziness. Epinephrine could be a good additive for high resorption blocks, like transversus abdominis plane (TAP) blocks. I have no experience with liposomal bupivacaine for nerve blocks. I am still waiting for good studies to convince me of its applicability to nerve blocks, but the future is promising since long-acting products are being developed—for example, capsaicin analogs to add to local anesthetics.

Dr Le-Wendling: Our theory is that if the block needs prolongation, place a continuous nerve block so that we can better control the duration. However, dexamethasone is the additive we use when patients are not suitable candidates for continuous nerve blocks. The literature suggests that lower doses (2-4 mg) are adequate. There does appear to be a greater duration for perineural dexamethasone when compared to systemic dexamethasone, by a few hours. Our goal is to prolong analgesia so that the block wears off in the morning as opposed to the middle of the night, since response to rebound pain in the middle of the night is much less timely. Epinephrine is sometimes used as an additive, mostly if we require regional vasoconstriction to minimize blood loss (eg, pterygopalatine block for sinus surgery). The literature on liposomal bupivacaine has been unconvincing in its stated benefits, especially in light of its cost. Our pharmacy has not approved its use.

Dr Lobo: I consider myself a catheter fan! Of course, it’s not a perfect technique, but its advantages are enormous when properly placed and managed. The problem in my country is that we haven’t got an ambulatory surgery system for catheter management at home. So, most ambulatory centers don’t place catheters. If the expected severe pain lasts less than 24 hours, I use adjuvants, IV dexamethasone being my favorite. I rarely use epinephrine as an extender. My experience with adjuvants is that their behavior can be very heterogeneous and unpredictable in a large number of cases. In Europe, liposomal bupivacaine is not approved.

Dr Ludwin: We do not routinely use epinephrine as a peripheral nerve block extender. With the use of ultrasound, the risk for intravascular injection is low, and using local anesthetics with epinephrine puts nerves at greater risk for nerve injury if there is an accidental intraneural injection. We do use dexamethasone for patients who would benefit from prolonged nerve blockade and analgesia, and have had good results. Continuous regional anesthesia by means of peripheral nerve catheters has proven to be a successful technique in providing prolonged postoperative analgesia. We do not have liposomal bupivacaine on formulary at this time.

Dr Vlassakov: We routinely use local anesthetic extenders when the expected severe pain trajectory exceeds 12 hours and when continuous nerve blockade is deemed unnecessary or contraindicated. Low-dose dexamethasone (2-4 mg in 20-40 mL of local anesthetic) and dexmedetomidine (up to 1 mcg/kg) are our most commonly used adjuncts at present. Through the years, we have also used clonidine and buprenorphine with some anecdotal success, but cost and logistical difficulties have tipped us in favor of the aforementioned agents. We use epinephrine at 1:400,000 dilution infrequently, mainly because of its systemic effects on absorption in our aging patient population. While we remain unconvinced that liposomal bupivacaine offers significant advantages over continuous blocks or even a local anesthetic–extender mix, we have been occasionally using liposomal bupivacaine/0.25% bupivacaine mixtures for single-shot fascial plane blocks such as rectus sheath, erector spinae plane, and TAP blocks, with some anecdotal success. We still favor continuous blocks when these are feasible and not contraindicated. At present, our outpatient catheter program is still very limited due to lack of a robust follow-up infrastructure.

5.Ultrasound guidance of regional anesthesia is here to stay. But what are the present and future roles of injection pressure monitoring, nerve stimulation, and other auxiliary measures in the safety of peripheral nerve blocks?

Dr Barrington: Injection pressure measurement established a presence for neurologic safety in monitoring for peripheral nerve blockade as a result of animal studies that linked intraneural (intrafascicular) injection pressures of 150 kPa or higher to persistent paralysis in canines. In the same experiments, extraneural injections had, on average, a lower mean opening injection pressure of less than 20 kPa.¹ Not all animal studies (admittedly with different methodologies) concur with these findings. For example, in a porcine model, low-pressure measurements occurred in intraneural (presumably extrafascicular) injections, and there was no correlation between the maximum volume injected or pressure generated and histologic evidence of nerve injury, which was present in 7 of 10 nerve specimens.² In another porcine study, the mean intraneural injection pressures, in the absence of intrafascicular injections, were low (average, 48 kPa, with significant variance); however, 2 out of 25 injections were associated with pressures exceeding those reported with intrafascicular injection.³

Human cadaveric models have also been used to differentiate intra- and extraneural injection; however, these studies do not distinguish between intrafascicular or extrafascicular (intraneural) injection. As might be expected, more compact nerves had higher injection pressures than nerves with greater abundance of connective tissue.^4,5 Most experiments have been performed in inanimate, animal, and human cadaveric models, and are not directly transferable to living humans.

The real clinical environment includes incremental injection and recurrent evaluation of the spread of local anesthetic, which is not replicated by existing bench studies. It would be easy to build the narrative that any new technology (injection pressure monitoring, impedance measurements, pressure waveforms, optical coherence tomography, acoustic cues) is associated with a high level of safety, assuming both existing procedural standards and a low incidence of block-related nerve injury apply. It may be impossible to determine decisively the ability of any one new device to improve patient outcomes after peripheral nerve blockade. The use of in-line proximal measurement of injection pressure reflects the whole system (including caliber and length of needle), and does not distinguish between pressure related to equipment and operator and the real pressure required to overcome tissue compliance.⁶ In-line proximal measurement increases with rate of injection and decreased needle caliber.⁷

One study reported that anesthesiologists were excellent at detecting even very subtle changes in resistance to injection,⁸ so perhaps this human factor should be given greater appreciation. My view is that more effort should apply to training and education as a whole, and in particular the use of ultrasound technology. Regardless of how sophisticated our assembled monitors appear, patient safety will continue to rely on meticulous attention to indication (anatomic, patient), anatomy, technique, and equipment. The importance of provider education and core skills development, situational awareness, adequate organization, preparation, nontechnical skills, standardized processes such as safety checklists, and routine patient follow-up will remain paramount.

Dr Gabriel: I think injection pressure monitoring and nerve stimulation still have some role, but they are definitely not as needed as much as they used to be. In the event of difficult anatomy (eg, morbidly obese patients), these tools can be useful to complement ultrasound guidance. Expert regionalists should still be skilled in these tools in order to tackle even the most difficult anatomy.

Dr Horn: Injection pressure monitoring is a good idea to minimize the risk for nerve injury. We all casually monitor injection pressure with the feedback received from the syringe plunger. The extra step and cost to connect a pressure-monitoring device has deterred me from its use.

Nerve stimulation at a low threshold—ie, less than 0.3 mAmp—as a possible marker of intraneural needle placement seems attractive, but is not convincing to me. More practical applications of stimulation include its use as a tool to confirm the proper nerve target when ultrasound visualization is difficult or to improve drug binding to the sodium channel. I use it routinely to confirm the level of needle placement for lumbar plexus block. Impedance to determine proximity to the nerve may be a better tool in the future.

Needle tracking, available with some ultrasound machines, carries great potential to minimize needle passes and reach the target directly. Tissue recognition with artificial intelligence may also assist us in the future.

Dr Le-Wendling: Considering that nerve injury may be not solely an issue of needle proximity but also of mechanical needle trauma, local anesthetic toxicity and other external factors (eg, limb positioning/tourniquet use), it is hard to speculate how impactful the use of injection pressure monitoring and nerve stimulation would be in preventing neurologic injury. High injection pressures can also result from the needle tip placed against connective tissue or bone or a clot within the needle, and are not representative of a subperineural intraneural needle tip placement. In addition, the use of animals to study neurologic injury may not be translatable into similar outcomes for humans since the microanatomy of the peripheral nervous system has been shown recently to be quite heterogeneous between different mammalian species.

Dr Lobo: This is a difficult question. Patient safety should be our main goal. But there’s no evidence that using injection pressure monitoring and nerve stimulation decreases the complication rate. The fact that these methods can fail too, means anesthesiologists don’t feel the need to use them all the time. I don’t have a monitor pressure in my hospital (I could use a simple technique to help monitor the pressure, but the risk for injecting air instead of local anesthetic is a concern), but the nerve stimulator is helpful whenever the ultrasound image is poor or the location of the nerve is deep.

Most importantly, in order to avoid complications and maintain safety, knowledge and experience (= competency) are fundamental. Medical education in regional anesthesia is extremely important and should start early during residency. Based on my experience, complications are directly proportional to inexperienced hands and success rates are proportional to experience. The behavior of “fresh” anesthesiologists with and without proper regional anesthesia education during their residency is completely different as those with this education have more tools to offer for patient care.

Dr Ludwin: Our standard practice is to dynamically scan the area of peripheral nerve blockade with ultrasound. This allows us to better understand the anatomy and anatomic variations for each patient. For patients with unclear anatomy following ultrasound guidance, the nerve stimulator is often used as a confirmatory technique. Familiarity with ease of injection and visualizing anesthetic spread under ultrasound minimizes the risk for intraneural injection.

Dr Vlassakov: Indeed, the disruptive innovation resulting from ultrasound guidance has led to the near disappearance from both clinical practice and teaching curricula of previously established techniques and methods of nerve localization, such as nerve stimulation, paresthesia, transarterial and landmark techniques. The fading role of nerve stimulation is now mostly limited to blocks where the individual sonoanatomy is less conducive to accurate target and needle identification, such as lumbar plexus blocks. Its role in preventing intraneural injection has always been debatable, and so is the role of injection pressure monitoring. In our practice, we consistently use nerve stimulation only in lumbar plexus blocks, but we routinely utilize a pressure monitoring device in most plexus and major nerve blocks, such as brachial and lumbar plexus blocks, and sciatic nerve blocks.

6.Should intentional intraneural injections still be subject to debate? How do you minimize nerve block risks?

Dr Barrington: Intentional intraneural injections should not be subject to debate. There is little doubt that intraneural, in particular intrafascicular, injection exposes axons to both mechanical injury and the cytotoxic effects of local anesthetics. We deliver local anesthetics to their extraneural target site in very high concentrations measured in millimoles. In contrast, other drugs are delivered to their target in micromolar or nanomolar concentrations.⁹ This sets up an unhealthy environment where nerves, even in the absence of mechanical injury, are at risk for chemical injury from local anesthetics. Investigators using a rat model demonstrated that intrafascicular injection of ropivacaine caused marked histologic abnormalities. However, both intraneural (extrafascicular) and extraneural (external to the epineurium) injections of ropivacaine were associated with similar but milder histologic abnormalities.¹⁰

Even an intraneural but extrafascicular injection may have a negative impact on the integrity of the peripheral nerve complex. Although the perineurium is the highly specialized protective layer of the peripheral nerve complex and is responsible for protecting the axons from injury, injecting into the extrafascicular compartment may injure the blood vessels that sustain the axons. There may also be some delayed fibrosis, and this may explain delayed onset of nerve injury. But why penetrate the outer border (epineurium) of the nerve, when we know that excellent results can be obtained if we inject external to this border?

We can minimize risks for block-related nerve injury by performing blocks without causing trauma to nerves and avoiding intraneural injection. Keep the needle tip away from the epineurium, be gentle with nerves, and only use the concentration of local anesthetic required to achieve the purpose of the block. Ultrasound guidance provides a unique tool because the needle tip and nerve can be imaged, guiding real-time feedback. I recommend that an incremental injection technique be used so as to assess the spread of local anesthetic external to the nerve.

Dr Gabriel: I personally do not have much experience with this approach, mainly because we have not had many problems with analgesia/surgical anesthesia with our sciatic nerve blocks, in terms of both block success and operating room efficiency. Why introduce a controversial concept into a system that already works?

Dr Horn: The debate on intraneural injection is not settled yet. We all agree that endoneurium/intrafascicular injection is a bad idea, but perineurium injection, within the epineurium, may not be universally rejected and may be considered acceptable within the context of low pressure, low volume, possibly lower concentration, and with no epinephrine. The debate should focus on what is an acceptable versus unacceptable site of injection for each block—ie, injecting local anesthetics between C5 and C6 within the superior trunk of the brachial plexus is often recommended but associated with a high incidence of paresthesia. Is that acceptable? The jury is still out.

To minimize risks, I stay away from direct contact with fascicles, use the lowest dose necessary, avoid a routine additive, prep the side with ChloraPrep (BD; chlorhexidine gluconate and isopropyl alcohol skin prep), always cover my probe, keep injection pressure low and monitor my patients for paresthesia and signs of local anesthetic systemic toxicity. No less critical is to decide with the patient when to do, and most important, when not to do a block.

Dr Le-Wendling: I believe it is always important to ask the question of which connective tissue layer should you breach in order to both minimize neurologic injury and provide an effective analgesic block. Unfortunately, modern ultrasound technology does not have the ability to clearly distinguish the epimysium from the circumneural sheath from the epineurium from the perineurium. We can speculate about the needle tip location from the spread of injectate. It appears that subcircumneural should be adequate for analgesic efficacy (although onset of anesthetic block will require patience), and that a subepineural block likely will not progress to more permanent neurologic injury with a faster block onset. However, if a quick onset (<30 minutes) is not necessary for surgical anesthesia, I would err on the side of being conservative and inject between the epineurium and circumneurium. If a surgical block is required in a high-risk patient with little time for onset, I will inject within the epineurium.

Dr Lobo: I don’t intentionally inject intraneurally. I don’t feel that achieving an intraneural injection is that crucial and clinically significant for shortening block onset time or sparing local anesthetic, honestly. The risks for causing a severe injury are still present. The fact that there are publications where intraneural injection was not associated with nerve damage can give us a false sense of safety. There is also an important aspect to consider: Nerve architecture is different as we travel along the nerve fiber towards the periphery. The neural tissue is more concentrated and compact close to the nerve’s origin. Performing an intraneural injection is riskier at the trunks of the brachial plexus than at the median nerve, for example. The risks from intraneural injection can be minimized by the way you approach the nerve structure: using a tangential needle approach instead of a direct approach; maintaining the tip of the needle under the ultrasound beam; and avoiding needle–nerve contact, which does not reduce success rate, although it might delay onset (not clinically significant).

Dr Ludwin: Conversations involving intentional intraneural injections need to be clear about how we are defining an intraneural injection. The nerve sheath is comprised of 3 layers: epineurium, perineurium, and endoneurium. The debate is whether or not subepineurial injections are safe. Ultrasound is not currently sensitive enough to distinguish between an intraneural injection that is extrafascicular (outside the perineurium) or intrafascicular (deep to the perineurium). The risk for nerve injury is much greater with an intrafascicular injection.

Nerve block risks are minimized in several ways. Dynamic ultrasound scanning allows for a better elucidation of nerve tissue versus other structures (eg, blood vessels, muscles, and tendons). The use of color flow can minimize risk for an intravascular injection. Careful aspiration and visualization of good spread of injectate around the desired target decreases the risk for an intravascular and intraneural injection. Familiarity with ease of injection minimizes risk for intraneural injection.

Dr Vlassakov: In my opinion, intentional intraneural injections should be strongly advised against. Yet, the devil is in the details: What do we define as intraneural? The macro- and microscopic anatomy of the different peripheral nerves varies significantly. While it is widely accepted as safe to inject local anesthetic beyond the thick sheath surrounding the sciatic nerve, intentional entry into any of the 2 distinct components within this sheath should not be endorsed.

What would the exact equivalents to para-, epi-, peri-, and endoneurium be in the sonoanatomy of the proximal brachial plexus and the major peripheral nerves, and are we capable of predictably and reproducibly identifying and avoiding discrete and vulnerable targets, such as neural fascicles and vasa nervorum? I believe that while the answers to these questions remain undetermined or negative, we should admire the delicate “nerve core” tissues from a safe distance only. In fact, even if safe entry was mechanically possible, the potential chemical insult from delivering concentrated local anesthetics beyond these protective layers should be prohibitive!

7.Getting practical: In a nutshell, what are your personal and your institutional perioperative analgesia prescriptions for total knee replacement (TKR), total hip replacement (THR), hip fracture, shoulder replacement, major thoracic surgery, major abdominal surgery, rib fracture, and mastectomy with or without reconstruction?

Dr Barrington: Clinical practice is evolving rapidly, with new techniques being described. Of course, multimodal oral analgesia is required in all cases. Ketamine is experiencing a resurgence in popularity.

TKR: Spinal anesthesia for the surgery and distal femoral triangle block for postoperative analgesia, using sonography to identify the apex of the femoral triangle,¹¹ injecting 1 to 2 cm proximal to this point. Using approximately a 30-mL volume of local anesthetic with ropivacaine 0.5% and additives described above: clonidine (75-100 mcg), buprenorphine (100-150 mcg), dexamethasone (2 mg). I would routinely use combined ultrasound guidance and nerve stimulation, with the latter to isolate and locate the nerve to the vastus medialis. My preference is to place the catheter close to this nerve and run an infusion with intermittent mandatory boluses. For posterior pain, I most commonly use a selective tibial block. I acknowledge that there is no perfect technique for this operation, and surgical infiltration is becoming more widely used.

THR: Spinal anesthesia for the surgery, followed by multimodal oral analgesia. Suprainguinal fascia iliaca block perhaps has a role, with a modest opioid-sparing effect. This surgery is not associated with a lot of pain, so I keep it simple.

Hip fracture: Spinal anesthesia for the surgery, followed by multimodal oral analgesia. Suprainguinal fascia iliaca block is indicated here, both for help with patient positioning for the surgery and for postoperative analgesia.

Total shoulder replacement: General anesthesia for the surgery and continuous interscalene block for postoperative analgesia. I am definitely not prescriptive here because of the increasing role of and evidence for dexmedetomidine as an adjunct, thereby increasing the duration of a single-injection technique. In addition, there are several variants that have potential, including the anterior approach to the suprascapular nerve (close to the omohyoid). Potentially, a suprascapular nerve block with a higher concentration of local anesthetic can be combined (to prolong duration of postoperative analgesia) with a more dilute local anesthetic concentration (thereby reducing motor block) for the traditional interscalene approach.

Rib fracture: Paravertebral or erector spinae block, with the latter becoming more popular because of ease of performance.

Mastectomy without reconstruction: Consider the so-called PEC (pectoralis nerve) II block, with approximately 0.2 mL/kg of ropivacaine 0.375% for injection between the pectoralis major and minor over the third rib and 0.25 mL/kg of ropivacaine 0.375% for injection between the pectoralis minor and serratus anterior over the fourth or fifth rib.

Mastectomy with reconstruction: Tissue expander—consider a PEC II block or an erector spinae block with catheter. Initial bolus is of 20 to 25 mL of ropivacaine 0.375%, followed by intermittent mandatory bolus of 20 mL of ropivacaine 0.2% every 4 to 6 hours. Tissue reconstruction such as the DIEP (deep inferior epigastric perforator) flap—consider an erector spinae block with catheter, as described above.

Dr Gabriel: Here is our institutional perioperative analgesia setup for the following major surgeries.

TKR: Use adductor canal catheters. For bilateral TKR, we use bilateral adductor canal catheters.

THR: We use no blocks.

Shoulder replacement: Use interscalene catheters.

Major thoracic surgery: Use epidural or paravertebral catheters.

Major abdominal surgery: Use epidural catheters.

Rib fracture: Use epidural, paravertebral, or intercostal cryoanalgesia.

Mastectomy: We use paravertebral catheters.

Our acute pain service—which consists mainly of regional anesthesiologists—follows all of these patients and, in addition to managing the block catheter, does multimodal opioid-sparing medical management in the pre-, intra-, and postoperative settings. We do not routinely perform PECs/serratus anterior/erector spinae plane blocks. It is something we do in cases when a paravertebral is contraindicated (eg, coagulopathy); however, based on our experience, the analgesia provided by paravertebrals is superior. We currently have a clinical trial comparing erector spinae plane block and paravertebral block for breast surgery.

Dr Horn: We created multimodal pathways for all routine surgeries with gabapentin, acetaminophen, celecoxib, dexamethasone, ketamine, and some form of regional/local anesthesia.

TKR: local infiltration and often adductor canal catheter, placed high.

THR: local infiltration and erector spinae catheter.

Hip fracture: femoral or fascia iliaca catheter.

Shoulder replacement: interscalene blocks and when phrenic nerve is to be spared, single-shot suprascapular nerve block with an erector spinae catheter.

Major thoracic surgery: epidural or paravertebral catheters.

Major abdominal surgery: epidural, sometimes paravertebral or TAP catheters.

Rib fracture: paravertebral or erector spinae catheters.

Mastectomy without reconstruction: various according to surgeons’ changing preferences, including paravertebral, rarely PECs, erector spinae, or just local infiltration.

Mastectomy with reconstruction: bilateral TAP or quadratus lumborum (QL) catheters for muscle flaps; considering erector spinae catheters. Personally, I am not a fan of PECs/serratus anterior plane blocks for breast cancer surgery as it is close to lymph nodes, whereas the paravertebral space is away from lymph nodes and can provide surgical anesthesia.

Dr Le-Wendling: We encourage all intraoperative management to include IV acetaminophen and ketorolac with or without ketamine, depending on the patient’s comorbidities.

TKR: femoral catheter and interspace between the popliteal artery and capsule of the posterior knee (iPACK) single shot; we send home with femoral catheter at 4 mL per hour of ropivacaine 0.2% on postoperative day (POD) 1 for 3 more days.

THR: femoral catheter (tunneled cephalad) with ropivacaine 0.2% 4 mL per hour (discharged home on POD 1 with femoral catheter to run for another 3 days), obturator single injection, and posterior hip local anesthetic deposition by surgical team intraoperatively.

Shoulder replacement: interscalene or cervical paravertebral catheter, bolused with 0.2% ropivacaine 10 mL running at 5 mL per hour, to be discharged on POD 1 with catheter for 3 more days.

Major thoracic surgery: thoracic epidural at T 5-6, ropivacaine 0.2% at 6 to 8 mL per hour with 4-mL boluses with patient-controlled epidural analgesia (PCEA) every 60 minutes.

Major abdominal surgery: thoracic epidural at T 6-8 (hepatectomy, pancreatectomy), low thoracic (colorectal surgery, abdominal hysterectomy), ropivacaine 0.2% at 6 to 8 mL per hour basal with 4-mL boluses via PCEA. Wean off 2 to 5 days after surgery, depending on patient tolerance of pain and PO status.

Rib fracture: thoracic paravertebral (1 catheter per 5 segments) for unilateral rib fractures or bilateral rib fractures, with contraindication of epidural placement. For bilateral rib fractures or in patients who have had recent exploratory laparotomy, add epidural analgesia (if not contraindicated).

Mastectomy: Use of PECs/serratus anterior plane blocks versus paravertebral blocks after breast surgery depends on the extent of surgery and the plan for coverage (analgesia vs anesthesia). Definitely use PEC I block for coverage of the pectoral muscles. The interfascial plane (PEC II/serratus plane) blocks are inconsistent in their coverage of the chest wall, but in obese patients, this allows for a greater degree of safety. I would do these for cosmetic surgery in obese patients.

Thoracic paravertebral blocks would only provide analgesia for the incisional (skin) pain and not the pain from underlying muscles. Therefore, thoracic paravertebral blocks would at best cover for simple mastectomies (with no involvement of the underlying muscles) or as an adjunct to blocks of the brachial plexus for bigger surgery. There is a greater risk for spinal/epidural blockade with their resultant hemodynamic changes. For bilateral surgery, thoracic paravertebral can potentially result in bilateral pneumothoraces, so I feel that its risk-to-benefit ratio is not reassuring. The one benefit is that the needle is placed farther away from the surgical field.

In major breast surgery (bilateral radical mastectomy), we prefer a high thoracic epidural, from T2-4. An epidural catheter covers much more dermatomal distribution for a much lower dose and volume of local anesthetic than a paravertebral block, allowing for bilateral spread, and this allows us to control the duration of analgesia. If our desire is to limit epidural dosing to minimize upper extremity weakness, then we add a PEC I block plus the serratus plane block.

Dr Lobo: My personal preference for perioperative analgesia is mainly multimodal analgesia (acetaminophen, NSAIDs, ketamine, and/or dexmedetomidine), having a regional analgesia technique as the main base strategy:

TKR: Use mainly a continuous femoral block (infusion pump with ropivacaine 0.2%, 5 mL/h with some motor block, if the surgeon does not mind), running for 2 days with an iPack block and acetaminophen plus NSAIDs.

THR: I normally do a single-shot femoral plus the lateral cutaneous nerve in the thigh, obturator blocks with ropivacaine 0.375%, and IV dexamethasone with NSAIDs.

Hip fracture: I do a fascia iliaca block before turning the patient for the spinal (for anesthesia) and multimodal analgesia.

Shoulder replacement: I start a continuous upper trunk brachial plexus catheter, preferentially before general anesthesia induction. I prefer general anesthesia because the position is quite uncomfortable and also based on surgeon’s preference.

Major thoracic surgery: I don’t do this kind of case nowadays, but I when I did, I was placing paravertebral blocks (single shot or continuous) for unilateral procedures. If I were doing these cases currently, I think I would use erector spinae plane blocks.

Major abdominal surgery: I still prefer a thoracic epidural. But in case of contraindications, I place bilateral QL blocks. I have no experience with continuous QL blocks.

Rib fracture: This depends on where the fracture is (posterior, lateral, or anterior arch) and the number of ribs involved, and whether it is a unilateral or bilateral condition. Having this in mind, I aim the point before the fracture. If it is in the posterior arch and it is unilateral, then I use a thoracic paravertebral block (TPVB), but continuous, especially in case of multiple ribs are involved. If there are more lateral or anterior fractures, I prefer fascial plane blocks as serratus anterior or erector spinae plane blocks. In case of bilateral, I would prefer a thoracic epidural, if possible; if not possible, then bilateral blocks (TPVB, serratus, or erector spinae plane) with special attention to the local anesthetic dosage, especially if using continuous techniques.

Mastectomy: I prefer PEC II (if axillary exploration) or PEC I (if no axillary intervention).

In the case of trauma patients, I normally sedate them before skin puncture, to avoid further discomfort and pain associated with the block placement. Sometimes positioning the patient can be very painful. My main goal is a good recovery from surgery (or trauma), so the pure awake regional anesthesia technique is not that important if the patient and/or the surgeon are not very comfortable with it.

Dr Ludwin: Of course, we always take into account risks and benefits for each patient, as well as patient preferences, but our typical “prescriptions” are the following.

TKR: perioperative multimodal analgesia, adductor canal blocks with or without iPACK blocks, spinal anesthesia, intraoperative sedation, and periarticular infiltration by the surgeon.

THR: perioperative multimodal analgesia, spinal anesthesia, intraoperative sedation, and periarticular infiltration by the surgeon.

Hip fracture: perioperative multimodal analgesia, preoperative femoral nerve blocks, spinal anesthesia, and intraoperative sedation.

Shoulder replacement: perioperative multimodal analgesia, interscalene/supraclavicular block with additives, and intraoperative sedation or general anesthesia.

Major thoracic surgery: perioperative multimodal analgesia, thoracic epidural anesthesia, or intercostal nerve blocks by the surgeons.

Major abdominal surgery: perioperative multimodal analgesia and, depending on surgical service and patient comorbidities, erector spinae, rectus, transversus abdominis, QL single-shot peripheral nerve blocks or catheters.

Rib fracture: perioperative multimodal analgesia and, depending on surgical service and patient comorbidities, intercostal, serratus, paravertebral blocks or catheters, and thoracic epidurals.

Mastectomy with or without reconstruction: perioperative multimodal analgesia and pectoral nerve blocks.

Dr Vlassakov: Our usual prescriptions are outlined below. Note we also give perioperative multimodal PO medications (mostly nonopioid) for all the procedures below, when not contraindicated.

TKR: spinal anesthesia, with preoperative high-volume distal adductor canal block with ropivacaine plus either dexamethasone or dexmedetomidine, followed by intraoperative pericapsular infiltration by the surgeons.

THR: spinal or general anesthesia, with intraoperative pericapsular infiltration by the surgeons.

Hip fracture: spinal or general anesthesia, and preoperative femoral/lateral femoral cutaneous or fascia iliaca blocks, combined with obturator nerve block in the case of hemi- or total arthroplasty.

Shoulder replacement: general anesthesia, with preoperative continuous interscalene block (1-2 days).

Major thoracic surgery: general anesthesia with predominance of thoracic epidural analgesia, with continuous paravertebral or proximal intercostal nerve blocks as backup in case of epidural failure or contraindications, plus intercostal nerve blocks by surgeons.

Major abdominal surgery: general anesthesia, and thoracic epidural analgesia with continuous TAP or rectus sheath blocks as backup in case of epidural failure or contraindications.

Rib fracture: continuous thoracic epidural or continuous nerve blocks of the paravertebral variety—paravertebral, retrolaminar, proximal intercostal, and erector spinae plane blocks.

Mastectomies without reconstruction: mostly general anesthesia with extensive local anesthetic infiltration by surgeons, sometimes substituted by multilevel single-injection paravertebral or proximal intercostal blocks.

Mastectomies with reconstruction: single-injection or continuous paravertebral or proximal intercostal nerve blocks, supplemented by single-injection PEC I blocks for tissue expanders or intraoperatively placed continuous ultrasound-guided TAP blocks for DIEP/TRAM (transverse rectus abdominis muscle) flap reconstruction.

References

1. Hadzic A, Dilberovic F, Shah S, et al. Combination of intraneural injection and high injection pressure leads to fascicular injury and neurologic deficits in dogs. Reg Anesth Pain Med. 2004;29(5):417-423.
2. Lupu CM, Kiehl TR, Chan VW, et al. Nerve expansion seen on ultrasound predicts histologic but not functional nerve injury after intraneural injection in pigs. Reg Anesth Pain Med. 2010;35(2):132-139.
3. Altermatt FR, Cummings TJ, Auten KM, et al. Ultrasonographic appearance of intraneural injections in the porcine model. Reg Anesth Pain Med. 2010;35(2):203-206.
4. Orebaugh SL, Mukalel JJ, Krediet AC, et al. Brachial plexus root injection in a human cadaver model: injectate distribution and effects on the neuraxis. Reg Anesth Pain Med. 2012;37(5):525-529.
5. Krol A, Vala A, Phylactides L, et al. Injection pressure mapping of intraneural vs. perineural injections: further lessons from cadaveric studies. Minerva Anestesiol. 2018;84(8):907-918.
6. Quadri C, Saporito A, Capdevila X. Real-time continuous monitoring of injection pressure at the needle tip for peripheral nerve blocks: description of a new method. Anaesthesia. 2018;73(2):187-194.
7. Patil J, Ankireddy H, Wilkes A, et al. An improvised pressure gauge for regional nerve blockade/anesthesia injections: an initial study. J Clin Monit Comput. 2015;29(6):673-679.
8. Claudio R, Hadzic A, Shih H, et al. Injection pressures by anesthesiologists during simulated peripheral nerve block. Reg Anesth Pain Med. 2004;29(3):201-205.
9. Hogan QH. Pathophysiology of peripheral nerve injury during regional anesthesia. Reg Anesth Pain Med. 2008;33(5):435-441.
10. Whitlock EL, Brenner MJ, Fox IK, et al. Ropivacaine-induced peripheral nerve injection injury in the rodent model. Anesth Analg. 2010;111(1):214-220.
11. Wong WY, Bjorn S, Strid JM, et al. Defining the location of the adductor canal using ultrasound. Reg Anesth Pain Med.2017;42(2):241-245.