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IntroductionProlonged tourniquet inflation during surgery frequently leads to tourniquet hypertension (TH), which is thought to arise from compression of A-δ fibers leading to sympathetically mediated C fiber activation. In the lower extremity, C fibers and other sympathetic nerve fibers are carried along the femoral artery. We hypothesized that blockade of these fibers at the femoral artery would decrease the incidence of TH.MethodsThirty American Society of Anesthesia 1–3 patients aged 18–75 undergoing total ankle arthroplasty were randomized to receive 15 mL of injectate (mepivacaine 1.5% or saline placebo) at the anteromedial aspect of the common femoral artery at the level of the inguinal crease under ultrasound guidance. Both groups received preoperative popliteal sciatic and saphenous nerve blocks for analgesia and a standardized general anesthetic. Esmolol was administered if systolic blood pressure rose >30% above baseline. Incidence of TH was the primary outcome.ResultsTH was present in 93.3% of sham patients versus 33.3% of block patients. Mean systolic pressure at 120 min and 150 min of tourniquet time was significantly higher in the sham group compared with the block group. Esmolol requirement (95.3+107.6 v 8.0+14.2, p=DiscussionUnder these experimental conditions, injection of local anesthetic around the femoral artery reduced the incidence of TH and intraoperative esmolol requirement.Trial registration numberwww.clinicaltrials.gov (NCT03390426; December 28, 2017).

Background and objectivesSeveral clinical studies have focused on assessing the effectiveness of different radiofrequency ablation (RFA) modalities in pain management. While a direct head-to-head clinical study is needed, results from independent studies suggest that water-cooled RFA (CRFA) may result in longer lasting pain relief than traditional RFA (TRFA). The primary purpose of this study was, therefore, to investigate in a preclinical model, head-to-head differences between the two RFA technologies.MethodsRFA was performed in a rat sciatic nerve model (n=66) in two groups: (1) TRFA or (2) CRFA. The surgeon was not blinded to the treatment; however, all the physiological endpoints were assessed in a blinded fashion which include histological, MRI, and nerve function assessment via electromyography.ResultsThe energy delivered by the generator for CRFA was significantly higher compared with TRFA. Histological staining of nerves harvested immediately following CRFA exhibited extended length and multiple zones of thermal damage compared with TRFA-treated nerves. MRI scans across 4 weeks following treatment showed edematous/inflammatory zones present for longer times following CRFA. Finally, there was greater attenuation and prolonged loss of nerve function measured via electromyography in the CRFA group.ConclusionsThis study shows that CRFA has greater energy output, as well as more pronounced structural and functional changes elicited on the peripheral nerves compared with TRFA. While these preclinical data will need to be confirmed with a large clinical randomized controlled trial, we are encouraged by the direction that they may have set for those trials.

Background and objectives Peripheral nerve block is an important component of the multimodal analgesia for total knee arthroplasty. Novel interventional techniques of ultrasound-guided nerve block supplying the posterior knee joint capsule require knowledge of the innervation of the posterior capsule. The objectives of this cadaveric study were to determine the course, frequency, and distribution of the articular branches innervating the posterior knee joint capsule and their relationships to anatomical landmarks. Methods Fifteen lightly embalmed specimens were meticulously dissected. The origin of articular branches was identified, their frequency recorded, and the course documented in relation to anatomical landmarks. The capsular distribution of articular branches was documented and a frequency map generated. Results In all specimens, articular branches from the posterior division of the obturator and tibial nerves were found to supply the posterior capsule. Additionally, articular branches from common fibular nerve and sciatic nerve were found in eight (53%) and three (20%) specimens, respectively. The capsular distribution of tibial nerve spanned the entire posterior capsule. The posterior division of obturator nerve supplied the superomedial aspect of the posterior capsule overlapping with the tibial nerve. The superolateral aspect of the posterior capsule was innervated by the tibial nerve and, when present, the common fibular/sciatic nerves. Conclusions Frequency map of the course and distribution of the articular branches and their relationship to anatomical landmarks form an anatomical basis for peripheral nerve block approaches that provide analgesia to the posterior knee joint capsule.

Background and Objectives Needle-induced nerve trauma and intraneural injection can lead to neurologic injury during peripheral nerve blocks. In this study, we assessed the utility of opening injection pressure (OIP), time to OIP, and rate of rise to OIP in detecting needle-nerve contact and intraneural injection. Methods Five common ultrasound-guided blocks of the femoral, saphenous, subgluteal sciatic, tibial, and common peroneal nerves were simulated in 10 fresh cadavers. Opening injection pressure was defined as peak psi in the 60-second interval during which the injection is initiated. Pressure-time curves were constructed separately for intraneural and perineural injections for each of the 5 nerves studied. Results Opening injection pressure was higher for intraneural than for perineural injections (P < 0.001), ranging from 21.5 psi (1111.9 mm Hg) to 25.8 psi (1334.2 mm Hg) for intraneural injections and from 3.8 psi (196.5 mm Hg) to 6.1 psi (315.5 mm Hg) for perineural injections. Time to OIP tended to be shorter for intraneural than for perineural injections, particularly for the subgluteal sciatic, tibial, and common peroneal nerves. Curves of intraneural injections had steep slopes with high peaks; curves of perineural injections had low slopes followed by plateaus. Rise to OIP was greater for intraneural than for perineural injections. Conclusions In our fresh human cadaver model, OIP detected intraneural needle placement. Monitoring of OIP could be useful in detecting and/or preventing intraneural injection during nerve blocks in the clinical setting. ispartof: Regional Anesthesia and Pain Medicine vol:42 issue:3 pages:362-367 ispartof: location:England status: published

Neuropathic pain is partially refractory to currently available treatments. Although some studies have reported that apoptosis signal-regulating kinase 1 (ASK1) may inhibit chronic pain, the mechanisms underlying this process have not been fully elucidated.Chronic constriction injury (CCI) of the rat sciatic nerve was used to establish a neuropathic pain model. Nociception was assessed using von Frey hair and Hargreaves' methods. Western blot and immunofluorescence were used to detect the cell signaling pathway. BV2 cell line was cultured for in vitro evaluation.Our results indicated that spinal ASK1 was co-expressed with the microglia marker ionized calcium binding adaptor 1. Additionally, intrathecal administration of ASK1 inhibitor suppressed the activation of spinal microglia and attenuated CCI-induced neuropathic pain. The ASK1 inhibitor also decreased the levels of phosphorylated ASK1 (p-ASK1), p65, p38 mitogen-activated protein kinase (MAPK) and tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) messenger RNA in lipopolysaccharide-stimulated BV2 microglia cells. Intragastric administration ofThis study showed that the expression of ASK1 in spinal microglia and ASK1 inhibitor suppressed microglia activation via suppression of p38 MAPK/NF-κB, which ultimately attenuated CCI-induced neuropathic pain.

To the Editor We thank Tedesco et al [1][1] for their interest in our ultrasound-guided lateral approach to the proximal sciatic nerve block.[2][2] We read their correspondence regarding the mid-shaft approach for sciatic nerve block with great interest. Based on their description, the average

To the Editor, We read with interest the investigation by Yoshida and collaborators,[1][1] published on the pages of this journal, on a lateral proximal approach to block the sciatic nerve in supine position. In experienced hands this technique holds the promise of minimizing mobilization of the

This prospective, randomized, double-blind study compared the effects of the ultrasound-guided popliteal sciatic nerve block performed by either intraneural or subparaneural approach followed by an electrophysiological evaluation. We hypothesized that intraneural injection provides a faster onset with a better success rate compared with the subparaneural approach.Eighty-eight patients were enrolled and randomized to receive an ultrasound-guided popliteal sciatic nerve block injecting 15 mL ropivacaine 1% according to an intraneural injection (group INTRA = 44) or a subparaneural injection (group SUBPARA = 44). The primary end point was the onset time of sensory and motor block, whereas secondary end points were successful, duration of the block, and the variation of the electrophysiological assessment after 5 weeks. The study was registered prior to patient enrollment (clinicaltrials.gov identifier NCT01987128).The median onset time for successful sciatic nerve block in the INTRA group was 10 (5-15 [5-30]) minutes versus 25 (15-35 [5-45]) minutes in the SUBPARA group (P0.001), with a rate of 41/43 (95.3%) compared with 25/40 (62.5%) in the SUBPARA group (P0.001). No difference was found regardless of the duration of the block. Fifty-three patients also performed the electrophysiological assessment at 5 weeks, showing a subclinical, significant reduction in amplitude of the action potentials with no difference between groups. No patients reported any clinical neurological complications after 6 months.In ultrasound-guided popliteal sciatic nerve block, intraneural injection provided a faster onset and better success rate compared with subparaneural. Both techniques resulted in a similar subclinical reduction in amplitude of the sciatic action potentials at 5 weeks after surgery. These findings should not be extended to other approaches.

Background and Objectives A chemically compatible, safe 4-drug multimodal formulation of bupivacaine combined with 3 adjuvants (clonidine, buprenorphine, and dexamethasone) has been proposed for long-lasting single-injection peripheral nerve blocks in patients. However, the relative importance of each of the adjuvants of the 4-drug formulation in producing long-lasting nerve blocks has not been determined. The aim of this study in rats was to determine which adjuvants (clonidine, buprenorphine, or dexamethasone) are essential for producing a long-lasting nerve block. Methods After baseline sensory and motor responses were recorded, 0.1 mL of drug solution was injected into the sciatic notch of rats. Animals were reevaluated at 10-minute intervals after injection for the absence or presence of sensory and motor response in the sciatic nerve. The 4-drug formulation of 0.25% bupivacaine plus all 3 adjuvants (clonidine, buprenorphine, and dexamethasone), 0.25% bupivacaine with 1 or 2 of the adjuvants added separately, and 0.25% bupivacaine alone were compared for duration of nerve block. Results The 4-drug multimodal solution produced a longer duration of sensory and motor nerve block than 0.25% bupivacaine alone (P Conclusions This animal study confirmed that the 4-drug multimodal formulation proposed for clinical nerve block produces superior duration of action compared to local anesthetic alone. This rat sciatic nerve model also indicated that one of the 3 adjuvants, clonidine, could by itself account for the extended duration of nerve block of bupivacaine.

Background and Objectives Percutaneous peripheral nerve stimulation (PNS) is an analgesic modality involving the insertion of a lead through an introducing needle followed by the delivery of electric current. This modality has been reported to treat chronic pain as well as postoperative pain the day following knee surgery. However, it remains unknown if this analgesic technique may be used in ambulatory subjects following foot procedures beginning within the recovery room immediately following surgery, and with only short series of patients reported to date, the only available data are derived from strictly observational studies. The purposes of this proof-of-concept study were to demonstrate the feasibility of using percutaneous sciatic nerve PNS to treat postoperative pain following ambulatory foot surgery in the immediate postoperative period and provide the first available data from a randomized controlled study design to provide evidence of analgesic effect. Methods Preoperatively, an electrical lead (SPRINT; SPR Therapeutics, Inc, Cleveland, Ohio) was percutaneously inserted posterior to the sciatic nerve between the subgluteal region and bifurcation with ultrasound guidance. Following hallux valgus osteotomy, subjects received 5 minutes of either stimulation or sham in a randomized, double-masked fashion followed by a 5-minute crossover period and then continuous stimulation until lead removal on postoperative days 14 to 28. Results During the initial 5-minute treatment period, subjects randomized to stimulation (n = 4) experienced a downward trajectory in their pain over the 5 minutes of treatment, whereas those receiving sham (n = 3) reported no such change until their subsequent 5-minute stimulation crossover. During the subsequent 30 minutes of stimulation, pain scores decreased to 52% of baseline (n = 7). Three subjects (43%) used a continuous popliteal nerve block for rescue analgesia during postoperative days 0 to 3. Overall, resting and dynamic pain scores averaged less than 1 on the numeric rating scale, and opioid use averaged less than 1 tablet daily with active stimulation. One lead dislodged, 2 fractured during use, and 1 fractured during intentional withdrawal. Conclusions This proof-of-concept study demonstrates that percutaneous sciatic nerve PNS is feasible for ambulatory foot surgery and suggests that this modality provides analgesia and decreases opioid requirements following hallux valgus procedures. However, lead dislodgement and fracture are concerns. Clinical Trial Registration This study was registered at Clinicaltrials.gov, identifier NCT02898103.

Background and objectivesPeripheral nerve block is an important component of the multimodal analgesia for total knee arthroplasty. Novel interventional techniques of ultrasound-guided nerve block supplying the posterior knee joint capsule require knowledge of the innervation of the posterior capsule. The objectives of this cadaveric study were to determine the course, frequency, and distribution of the articular branches innervating the posterior knee joint capsule and their relationships to anatomical landmarks.MethodsFifteen lightly embalmed specimens were meticulously dissected. The origin of articular branches was identified, their frequency recorded, and the course documented in relation to anatomical landmarks. The capsular distribution of articular branches was documented and a frequency map generated.ResultsIn all specimens, articular branches from the posterior division of the obturator and tibial nerves were found to supply the posterior capsule. Additionally, articular branches from common fibular nerve and sciatic nerve were found in eight (53%) and three (20%) specimens, respectively. The capsular distribution of tibial nerve spanned the entire posterior capsule. The posterior division of obturator nerve supplied the superomedial aspect of the posterior capsule overlapping with the tibial nerve. The superolateral aspect of the posterior capsule was innervated by the tibial nerve and, when present, the common fibular/sciatic nerves.ConclusionsFrequency map of the course and distribution of the articular branches and their relationship to anatomical landmarks form an anatomical basis for peripheral nerve block approaches that provide analgesia to the posterior knee joint capsule.

Background and Objectives Dexmedetomidine is known to have neural protection effect via attenuation of inflammatory responses induced by local anesthetics. We investigated whether intraneural dexmedetomidine is effective for attenuating or preventing neural injury resulting from inadvertent intraneural injection of local anesthetic. Methods Rats were randomly divided, and left sciatic nerve was surgically exposed. The rats received no injection (control group) or intraneural injections of 0.2 mL of normal saline (saline group), 0.2 mL of 0.5% ropivacaine (ropivacaine group), or 0.2 mL of 0.5% ropivacaine and 0.5 μg/kg of dexmedetomidine (ropivacaine plus dexmedetomidine group). Interleukin (IL)-6 and IL-1β messenger RNA (mRNA) levels were detected at 60 minutes after intraneural injection in experiment 1 (5 per group). Sensory and motor functions were assessed until the return of normal sensory and motor functions, and histopathological and ultrastructure analysis were performed at 4 weeks after intraneural injection in experiment 2 (8 per group). Results Dexmedetomidine with ropivacaine better enhanced sensory and motor blockade than ropivacaine alone. IL-6 (3.2 ± 1.0 vs 5.9 ± 2.1), IL-1β (1.1 ± 0.1 vs 2.2 ± 0.7) levels, scores of axon and myelinated fiber degeneration (1 [0–2] vs 2 [1–3]), and demyelinated fiber percentages (20.1 ± 10.4 vs 48.3 ± 12.7) were lower in the ropivacaine plus dexmedetomidine group than in the ropivacaine group. No animals showed any signs of permanent neurological deficit. Conclusions Intraneural dexmedetomidine has sensory and motor blockade-enhancing effects, anti-inflammatory properties, and protective effects against neural injury. These findings suggest that dexmedetomidine as an adjuvant has beneficial effects in rat when intraneural injection of local anesthetic occurs.

This prospective randomized trial compared ultrasound-guided single-injection (SI) and triple-injection (TI) subparaneural popliteal sciatic nerve block. We hypothesized that multiple injections are not required when local anesthetic (LA) is deposited under the paraneurium because the latter entraps LA molecules, ensuring circumferential spread around the nerve. Therefore, in addition to comparable success rates, we also expected similar total anesthesia-related times (sum of performance and onset times) and designed this study as an equivalency trial.Ultrasound-guided subparaneural posterior popliteal sciatic nerve block was carried out in 100 patients. In the SI group, LA was deposited at a single location between the tibial and peroneal nerves. In the TI group, LA was injected between the tibial and peroneal divisions, medial to the tibial nerve, and lateral to the common peroneal nerve. The total LA volume (15 mL) and mixture (lidocaine 1%-bupivacaine 0.25%-epinephrine 5 μg/mL) were identical in all subjects. The performance time, number of needle passes, and adverse events (paresthesia, neural edema) were recorded by the (nonblinded) investigator supervising the block. A blinded observer evaluated the success rate (sensorimotor composite score ≥6/8 points at 30 minutes) as well as the onset time and contacted patients 7 days after the surgery to inquire about persistent numbness or motor deficit.Both techniques provided comparable success rates (92%) and total anesthesia-related times (17.1-19.7 minutes). Expectedly, the SI group required fewer needle passes (1 vs 3; P0.001) and a shorter needling time (3.0 ± 2.3 minutes vs 4.0 ± 2.3 minutes; P = 0.025). The TI group displayed a shorter onset time (12.5 ± 7.9 minutes vs 15.8 ± 7.9 minutes; P = 0.027). The performance time, procedural discomfort, and incidence of paresthesia (14%-20%) were similar between the 2 groups. Sonographic neural swelling was detected in 2 subjects in the SI group. In both cases, the needle was carefully withdrawn and the injection was completed uneventfully. Follow-up of the 100 subjects 1 week after surgery revealed no residual numbness or motor deficit.Ultrasound-guided SI and TI subparaneural popliteal sciatic nerve blocks result in comparable success rates and total anesthesia-related times. Expectedly, the SI technique requires fewer needle passes.

Background and Objectives Sciatic nerve block provides analgesia after foot and ankle surgery, but block duration may be insufficient. We hypothesized that perineural dexamethasone and buprenorphine would reduce pain scores at 24 hours. Methods Ninety patients received ultrasound-guided sciatic (25 mL 0.25% bupivacaine) and adductor canal (10 mL 0.25% bupivacaine) blockade, with random assignment into 3 groups (30 patients per group): control blocks + intravenous (IV) dexamethasone (4 mg) (control); control blocks + IV buprenorphine (150 μg) + IV dexamethasone (IV buprenorphine); and nerve blocks containing buprenorphine + dexamethasone (perineural). Patients received mepivacaine neuraxial anesthesia and postoperative oxycodone/acetaminophen, meloxicam, pregabalin, and ondansetron. Patients and assessors were blinded to group assignment. The primary outcome was pain with movement at 24 hours. Results There was no difference in pain with movement at 24 hours (median score, 0). However, the perineural group had longer block duration versus control (45.6 vs 30.0 hours). Perineural patients had lower scores for “worst pain” versus control (median, 0 vs 2). Both IV buprenorphine and perineural groups were less likely to use opioids on the day after surgery versus control (28.6%, 28.6%, and 60.7%, respectively). Nausea after IV buprenorphine (but not perineural buprenorphine) was severe, frequent, and bothersome. Conclusions Pain scores were very low at 24 hours after surgery in the context of multimodal analgesia and were not improved by additives. However, perineural buprenorphine and dexamethasone prolonged block duration, reduced the worst pain experienced, and reduced opioid use. Intravenous buprenorphine caused troubling nausea and vomiting. Future research is needed to confirm and extend these observations.

In the gluteal and thigh region, the arteria comitans accompanies the sciatic nerve for a short distance, then penetrates the nerve and runs to the lower part of the thigh. There is no study that recognizes this artery as a guide to the location of the sciatic nerve. In this report, we describe a series of 6 knee arthroplasty patients in whom ultrasound-guided sciatic nerve block was successfully performed using color Doppler and pulsed wave Doppler to visualize the arteria comitans as a guide to the location of the sciatic nerve. We have found that detecting the arteria comitans as a landmark is novel and may offer an additional tool with the existing methods for sciatic nerve block.

Background and Objectives The aim of this study was to analyze histological nerve toxicity of perineural dexamethasone administration in combination with ropivacaine on mice. Efficacy of perineural dexamethasone in combination with regional anesthesia is clearly demonstrated. However, the safety of this procedure is still a matter of debate. Methods A sciatic nerve block was performed on 90 mice. Five groups, each containing 18 mice assigned randomly, were used in these experiments: the sham group (isotonic saline solution), R group (perineural ropivacaine), D group (perineural dexamethasone), RDPN group (perineural ropivacaine and perineural dexamethasone), and the RDS group (perineural ropivacaine and systemic dexamethasone). Sensory and motor blocks were evaluated every 30 minutes for 14 hours. Fourteen and 28 days after this procedure, 9 mice in each group were killed for sciatic nerve histological assessment. Results No statistical difference was observed between different groups for Wallerian degeneration (P = 0.28 at day 14 and P = 0.22 at day 28) and perineural inflammation (P = 0.9 at day 14). Motor and sensory block durations were tested for each group. A statistical difference was observed for motor block duration between the RDPN group (150 minutes [127–172 minutes]), the RDS group (120 minutes [90–120 minutes]), and the R group (60 minutes [60–90 minutes]). Sensory block duration was also statistically different: 660 minutes (660–720 minutes) in the RDPN group, 480 minutes (427–660 minutes) in RDS group, 330 minutes (240–410) in the R group. Conclusions A combination of ropivacaine and perineural dexamethasone allows longer sensory block duration compared with ropivacaine alone or ropivacaine and systemic dexamethasone, without increased neural toxicity.

Background and Objectives The aim of this study was to determine the minimum effective volume (MEV) of combined lidocaine 1.0%–bupivacaine 0.25% with epinephrine 5 μg/mL in 90% of patients (MEV90) for ultrasound-guided subparaneural popliteal sciatic nerve block. Methods All subjects received an ultrasound-guided subparaneural popliteal sciatic nerve block (at the neural bifurcation) with combined lidocaine 1.0%–bupivacaine 0.25% and epinephrine 5 μg/mL. Using an out-of-plane technique, a 17-gauge, 8-cm Tuohy needle was advanced until its tip was positioned between the tibial and peroneal nerves inside the paraneural sheath. Volume assignment was carried out using a biased coin design, up-and-down sequential method, where the volume of local anesthetic administered to each patient depended on the response of the previous one. In case of failure, the next subject received a higher volume (defined as the previous volume with an increment of 3.0 mL). If the previous patient had a successful block, the next subject was randomized to a lower volume (defined as the previous volume with a decrement of 3.0 mL), with a probability of b = 0.11, or the same volume, with a probability of 1 – b = 0.89. Using a composite scale encompassing sensory and motor block, success was defined, at 30 minutes, as a minimal score of 6 points (out of 8 points). The 6-point score was intended to mirror successful postoperative analgesia. Patients undergoing surgery of the leg, ankle, or foot were prospectively enrolled until 45 successful blocks were obtained. Results Fifty-two patients were recruited for this study. Using isotonic regression and bootstrap confidence interval, the MEV90 of combined lidocaine 1.0%–bupivacaine 0.25% with epinephrine 5 μg/mL was estimated to be 13.3 mL (95% confidence interval, 10.2–16.4 mL). Conclusions For ultrasound-guided subparaneural (analgesic) popliteal sciatic nerve block, the MEV90 of combined lidocaine 1.0%–bupivacaine 0.25% with epinephrine 5 μg/mL is 13.3 mL (95% confidence interval, 10.2–16.4 mL).

Background and Objectives Neuropathic pain is related to the sustained activation of neuroglial cells and the production of proinflammatory cytokines in the spinal dorsal horn. Ghrelin, the endogenous ligand for growth hormone secretagogue receptor 1a (GHSR-1a), has been shown to inhibit the activation of microglia and the release of proinflammatory cytokines. The purpose of this study was to investigate the role of ghrelin/GHSR-1a signaling in neuropathic pain and to understand the associated mechanisms. Methods A rat model of neuropathic pain was established by chronic constriction injury (CCI) of the sciatic nerve. Hyperalgesia and allodynia were evaluated by observing the mechanical withdrawal threshold and the thermal withdrawal latency. The expression levels of ghrelin and GHSR-1a were detected by semiquantitative reverse transcriptase–polymerase chain reaction and Western blot analysis. The levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α were detected using an enzyme-linked immunosorbent assay. The expression levels of p-p38 mitogen-activated protein kinases (p38 MAPK) and nuclear factor-κB (NF-κB) p65 were determined by Western blot and immunohistochemistry analysis. Results Both ghrelin and GHSR-1a were expressed in the spinal dorsal horns of normal rats and were not significantly different from that of sham rats. However, rats in the CCI model group developed severe hyperalgesia and allodynia, as well as significantly downregulated expression of ghrelin and GHSR-1a. Compared with CCI model rats, intrathecal injection of ghrelin clearly delayed thermal hyperalgesia and mechanical allodynia at 3, 5, and 7 days after CCI; reduced the levels of IL-1β, IL-6, and tumor necrosis factor-α; and inhibited the phosphorylation of p38 MAPK and the activation of NF-κBp65 in the spinal dorsal horn. In addition, the effect of ghrelin could be blocked by [D-Lys3]-GHRP-6, a GHSR-1a antagonist. Conclusions Our present study demonstrated that ghrelin alleviated neuropathic pain through a GHSR-1a–mediated suppression of the p38 MAPK/NF-κB pathway.

Background The ideal spread of local anesthetic for effective, rapid, and safe sciatic nerve block is debated. We hypothesized that subparaneural ultrasound-guided injection results in faster onset and has a better success rate than extraneural circumferential spread. Methods Patients undergoing elective tibial, foot, and ankle surgery with popliteal sciatic nerve blocks were prospectively enrolled. After randomization, the needle tip position was adjusted to ensure circumferential extraneural or subparaneural spread; 0.3 mL/kg of mepivacaine 10 mg/mL was injected. Post hoc video analysis was used to group the patients according to extraneural, subparaneural, and unintentional intraepineural spread. Results There were 26 (43.3%) patients in the subparaneural group and 22 (36.7%) in the extraneural group. Block onset time was shorter in the subparaneural group than in the extraneural group (11 [3–21] minutes; mean [95% confidence interval], 11 [8.97–13.02] minutes and 17 [6–30] minutes; mean [95% confidence interval] 18.37 [14.17–22.57] minutes, respectively; P = 0.002). The duration of sensory blockade increased (397 [178–505] minutes vs 265 [113–525] minutes; P = 0.04). The success rate of the block also increased. Unintentional intraepineural injection occurred in 8% of patients (3 patients in the subparaneural group and 1 patient in the extraneural group; NS). Block onset time was shorter than for the subparaneural and extraneural groups (6 [3–12] minutes, 12 [3–21] minutes, and 18 [6–30] minutes; P = 0.01). Conclusions A subparaneural injection accelerated the onset time and increased the duration of tibial nerve sensory blockade compared with circumferential extraneural injection. With unintentional intraepineural spread, the onset time was significantly shorter than for the other groups.

Perineural hematoma may occur during performance of peripheral nerve blocks. The aim of this study was to test the hypothesis that an iatrogenic hematoma in the immediate vicinity of a peripheral nerve may cause histologic evidence of nerve injury.Fifty milliliters of autologous blood was injected adjacent to the right sciatic nerve in 20 anesthetized female pigs. In order to discern between blood-related volume and immune effects, 50 mL of albumin was injected at the same location in an additional 22 pigs. Either blood or albumin was injected in random order. The left sciatic nerve served as a negative control in all animals, that is, either no needle placement or needle placement without injection. After 48 hours, the nerves were resected. The grade of nerve injury was scored from 0 (no injury) to 3 (severe injury) by histologic analysis of myelin tissue and inflammatory cells.Eighty-two nerve specimens were examined. Injury scores were significantly (P0.01) higher in the blood injection (n = 20; median [interquartile range] 2 [2-2]) and albumin injection (n = 22, 1 [1-2]) conditions compared with the no needle placement (n = 22, 0 [0-1]) and "dry needle placement" (n = 20, 1 [0-1]) conditions. Widespread inflammatory changes were seen in the blood injection group, in which 15% of nerve specimens showed damage to myelin.Our data suggest that hematoma adjacent to nerve tissue may result in structural nerve injury and inflammatory changes.

Background and Objectives: When one is performing ultrasound-guided peripheral nerve blocks, it is common to inject a small amount of fluid to confirm correct placement of the needle tip. If an intraneural needle tip position is detected, the needle can then be repositioned to prevent injection of a large amount of local anesthetic into the nerve. However, it is unknown if anesthesiologists can accurately discriminate intraneural and extraneural injection of small volumes. Therefore, this study was conducted to determine the diagnostic accuracy of ultrasound assessment using a criterion standard and to compare experts and novices in ultrasound-guided regional anesthesia.Methods: A total of 32 ultrasound-guided infragluteal sciatic nerve blocks were performed on 21 cadaver legs. The injections were targeted to be intraneural (n = 18) or extraneural (n = 14), and 0.5 mL of methylene blue 1% was injected. Cryosections of the nerve and surrounding tissue were assessed by a blinded investigator as "extraneural" or "intraneural." Ultrasound video clips of the injections were reviewed by 10 blinded observers (5 experts, 5 novices) independently who scored each injection as either "intraneural," "extraneural," or "undetermined."Results: The mean sensitivity of experts and novices was measured to be 0.84 (0.80-0.88) and 0.65 (0.60-0.71), respectively (P = 0.006), whereas mean specificity was 0.97 (0.94-0.98) and 0.98 (0.96-0.99) (P = 0.53).Conclusions: Discrimination of intraneural or extraneural needle tip position based on an injection of 0.5 mL is possible, but even experts missed 1 of 6 intraneural injections. In novices, the sensitivity of assessment was significantly lower, highlighting the need for focused education.

To the Editor:We appreciate the interest expressed by Coraci et al1 in our article, “The Lateral Femoral Cutaneous Nerve: Description of the Sensory Territory and a Novel Ultrasound-Guided Nerve Block Technique” presenting a novel ultrasound-guided lateral femoral cutaneous (LFC) nerve block techniq

Background and Objectives This is a follow-up to determine long-term outcomes after total knee arthroplasty (TKA) in patients enrolled in a previous randomized trial that found reduced postoperative pain after addition of sciatic nerve block to continuous femoral nerve block for TKA. Methods Physical function after TKA was evaluated at 3 and 12 months in patients (n = 89) receiving continuous femoral nerve block alone (group F), combined with a single-injection (group Fs) or continuous sciatic nerve block (group FCS) after TKA, until the second postoperative day. Physical function, stiffness, and pain were measured by using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Oxford Knee Score 12-item knee questionnaires, and visual analog scale at rest and during mobilization before TKA and 3 and 12 months afterward. Post hoc, a median split on poor functioning (WOMAC) was analyzed. Results Western Ontario and McMaster Universities Osteoarthritis Index, Oxford Knee Score 12-item knee, and visual analog scale scores improved significantly in all patients, without any differences among groups. Median (range) WOMAC at 3 months were in group F, 83 (20–97); group Fs, 72 (25–99); and group, FCS 76 (28–100) and at 12 months 87 (35–98), 77 (43–100), and 89 (35–100), respectively. Conclusions No differences were detected in the secondary outcomes we examined. Thus, improved postoperative outcome did not translate into improved functional outcome or long-term pain.

Before bifurcation, the sciatic nerve is composed of 2 component nerves encased in a common investing extraneural layer (CIEL). We examined the effect of various volumes injected beneath the CIEL on the success and duration of sciatic nerve block.Ultrasound-guided nerve-stimulator-assisted sciatic nerve blocks were performed on 142 subjects. Subjects were randomized into 14 groups (0.5% ropivacaine or bupivacaine) with epinephrine 1:300,000 in volumes ranging from 2.5 to 30 mL. Successful block was defined as a complete sensory and motor block at 60 minutes. The minimum threshold current, time to complete block, duration of sensory and motor block, postoperative pain, and analgesic requirements were recorded.The mean threshold current external to the CIEL was 0.52 (0.15) mA compared to 0.19 (0.09) mA beneath the CIEL (P0.001). Successful block was achieved in 30 of 40 subjects that received 5 mL or less of ropivacaine or bupivacaine compared with 97 of 99 that received 10 mL or greater volume (P = 0.006). Injection volumes greater than or equal to 10 mL produced complete sensory and motor block within 30 minutes. Volumes greater than 10 mL did not extend the duration of the sensory or motor block. Injection volumes of 2.5 and 5 mL were associated with delayed onset and decreased block duration and a greater fraction of subjects experiencing pain behind the knee.Injecting 10 mL of 0.5% bupivacaine or ropivacaine below the CIEL produces comparable onset and duration of sensory and motor blockade as volumes as large as 30 mL.

Objective Necrotizing fasciitis is an infection of the soft tissue that is characterized by rapidly spreading inflammation and subsequent necrosis. It is a rare complication of peripheral nerve blocks. We report a rare case of necrotizing fasciitis after placement of a peripheral nerve catheter. Case Report A 58-year-old woman presented for an elective right second metatarsal resection and received a sciatic nerve catheter for postoperative pain control. On postoperative day 7, clinical examination and imaging supported the diagnosis of necrotizing fasciitis. Conclusions Multiple reports have been published of necrotizing fasciitis after single-shot peripheral nerve block injections, neuraxial anesthesia, and intramuscular injections. This case highlights the potential for the rare complication of necrotizing fasciitis after peripheral nerve catheter placement.

Background and Objectives Selecting an appropriate anesthetic technique for patients with ankylosing spondylitis undergoing hip surgery is challenging because of a potentially difficult airway, the risk of cardiovascular and respiratory complications, and the technical difficulty of performing central neuraxial blocks in patients with ankylosing spondylitis. Our objective was to report a case in which combination neural blockade was used successfully in an elderly patient with ankylosing spondylitis undergoing hip fracture surgery. In addition, a literature review of the anesthetic techniques reported for these patients was conducted. Case Report A 70-year-old man with severe ankylosing spondylitis and respiratory dysfunction was scheduled for a closed intertrochanteric fracture reduction and internal fixation. Combined fascia iliaca block and parasacral sciatic nerve block were used successfully for the surgery. Postoperative analgesia was accomplished by continuous fascia iliaca block. Conclusions According to the literature review, general anesthesia is the most commonly performed anesthetic technique for patients with ankylosing spondylitis undergoing hip surgeries. Special intubation techniques and cautious airway management were very important for these patients. Although both general anesthesia and central neuraxial blockade pose considerable risks to the patients, this case report suggests that combined fascia iliaca block and sciatic nerve block might be a promising option.

Quaternary lidocaine derivatives (QLDs) have recently received much attention because of their potential application in prolonged or sensory-selective local anesthesia. However, associated tissue toxicity is an impeding factor that makes QLDs unfavorable for clinical use. Based on the proposed intracellular site of action, we hypothesized that nerve blocks obtained from lower concentrations of QLDs would be enhanced by the coapplication of extracellularly acting site 1 sodium-channel blocker, resulting in prolonged block duration but with minimal tissue toxicity.Quaternary lidocaine derivatives (QX-314 or QX-222), site 1 sodium-channel blockers (tetrodotoxin [30 μM] or saxitoxin [12.5 μM]), or both were injected in the vicinity of the sciatic nerve. Thermal nociceptive block was assessed using a modified hot plate test; motor block by a weight-bearing test. Tissue from the site of injection was harvested for histological assessment.Coapplication of 25 mM QX-314 or 100 mM QX-222 with site 1 sodium-channel blockers produced an 8- to 10- fold increase in the duration of nerve blocks (P0.05), compared with QLDs or site 1 blockers alone. Quaternary lidocaine derivatives elicited severe myotoxicity; this was not exacerbated by coinjection of the site 1 sodium-channel blockers.Coadministration of site 1 sodium-channel blockers and QLDs greatly prolongs the duration of peripheral nerve block without enhancing local tissue injury, but minimal myotoxicity still persists. It is not clear that the risks of QLDs are outweighed by the benefits in providing prolonged nerve blockade.

Background The present study was conducted to determine the incidence of unintentional intraneural injection during ultrasound-guided subgluteal sciatic nerve block using a low-frequency transducer. We also observed the effects of intraneural injection using ropivacaine and mepivacaine. Methods Enrolled in the study were 325 patients undergoing arthroscopic knee surgery, who each received a subgluteal sciatic nerve block under ultrasound guidance using 1.5% mepivacaine with 1:400,000 epinephrine or 0.5% ropivacaine. A block needle was inserted in-plane with the ultrasound transducer (5-2 MHz curved array) and advanced slowly under real-time ultrasound guidance until it was positioned immediately adjacent to the nerve. Twenty milliliters of either anesthetic was then injected to produce a circumferential spread. An ultrasound video was recorded and used to examine whether the local anesthetic was injected intraneurally. Sensory and motor blockade was evaluated for 30 mins after completion of the block. Duration of the block and any neurologic complications were also examined. Results Intraneural injection was detected in 46 patients (16.3%; 95% confidence interval, 12.3%–20.3%). Onset of sensory and motor blockade was significantly faster in patients with intraneural injection than those without either mepivacaine or ropivacaine. Duration of sensory blockade was similar between patients with and without intraneural injection. No patient developed postoperative neurologic complications. Conclusions Unintentional intraneural injection occurred at an incidence rate of 16.3% for the ultrasound-guided subgluteal approach to the sciatic nerve. Intraneural injection of mepivacaine or ropivacaine hastened the onset of blockade but did not affect block duration, and it did not result in clinical neural injury in our small sample of patients.

Background and Objectives To minimize acute postoperative pain, a new formulation of slowly released bupivacaine was developed. Methods Bupivacaine was microencapsulated at 60% (wt/wt) in poly-lactide-co-glycolide polymers and characterized for physicochemical properties and bupivacaine release kinetics. This formulation was injected around the rat sciatic nerve to produce an antinociceptive effect to toe pinch. Mechanical hyperalgesia following lateral plantar paw incision in rats was assessed for 7 to 14 days when the bupivacaine slow-release formulation was placed at the ipsilateral sciatic nerve and compared with the hyperalgesia that developed with various controls. Results Bupivacaine was released in vitro at a relatively constant rate over a period of ∼72 to 96 hours. Complete antinociception, shown as no response to toe pinch, lasted for 23 ± 7 hours, with a half-recovery time of 42 ± 8 hours after sciatic nerve injection of 0.4 mL of the microspheres delivering 34 mg of bupivacaine. Solutions of 0.5% (wt/vol) bupivacaine-HCl (0.1 mL) produced complete antinociception for less than 2 hours and recovery half-times of 2 hours. Postincisional mechanical hyperalgesia, shown by increased withdrawal responses to von Frey filaments, was absent for 24 hours and was lower than control for 96 hours, when the sciatic nerve was blocked by bupivacaine microspheres, whereas the 0.5% bupivacaine solution reduced postincisional pain for only 4 hours. Conclusions Corresponding to its far greater functional blocking time, the microsphere-bupivacaine formulation was able to significantly reduce postoperative pain below control levels for up to 4 days. These findings of several days of postoperative pain relief, for an injectable formulation containing a single active agent, present an improved and potentially promising therapy to prevent acute pain after surgery.

Background and Objectives Ultrasound needle visualization is a fundamental skill required for competency in ultrasound-guided regional anesthesia. The primary objective of this study using a cadaver model was to quantify the number of procedures that novices need to perform before competency, using a predefined dynamic scoring system was achieved in ultrasound needle visualization skills. Methods Fifteen trainees, novices to ultrasound-guided regional anesthesia, performed 30 simulated sciatic nerve blocks in cadavers. After each procedure, a supervisor provided feedback regarding quality-compromising behaviors. Learning curves were constructed for each individual trainee by calculating cusum statistics. Trainees were categorized into those who were proficient, not proficient, and undetermined. A mathematical model predicted the number of procedures required before an acceptable success rate would be attained. Logistic regression was used to identify factors associated with success. Results There was wide variability in individual cusum curves. The mean number of trials required to achieve competency in this cohort was 28. Trainees were categorized as proficient (n = 6), not proficient (n = 5), and undetermined (n = 4). With each subsequent procedure, there was a significant increase in the likelihood of success for trainees categorized as not proficient (P = 0.023) or undetermined (P = 0.024) but not for trainees categorized as proficient (P = 0.076). Participants recruited later in the study had an increased likelihood of success (P Conclusions Trainees became competent in ultrasound needle visualization at a variable rate. This study estimates that novices would require approximately 28 supervised trials with feedback before competency in ultrasound needle visualization is achieved.

Sciatic nerve block fails in preventing the development of late stress-induced hyperalgesia (SIH) when high-dose fentanyl is administered perioperatively in rats.The aim of our study was to evaluate the effect of regional anesthesia (RA) on hyperalgesia and long-term pain vulnerability after surgery in rats exposed or not to high doses of fentanyl intraoperatively.Experiment 1 evaluated the effects of D0 RA on hyperalgesia after incision and on the variations of nociceptive threshold (NT) after non-nociceptive environmental stress (NNES) at D10. Four groups were compared: control K1 (saline in sciatic nerve catheter, no plantar surgery), I (incision: saline in sciatic nerve catheter and plantar surgery), ISSR (incision-single-shot ropivacaine: single-shot ropivacaine, plantar surgery), and IMSR (incision-multiple-shot ropivacaine: 1 shot of ropivacaine, plantar surgery, and then 3 more ropivacaine injections every 2 h). Experiment 2 evaluated the effects of D0 RA (4 injections) on NT variations after surgery (D1-D10) and after stress (D10) in rats treated with fentanyl at the time of surgery (FI and FIMSR groups).Postoperative hyperalgesia lasted for 7, 4, and 2 days for groups I, ISSR, and IMSR, respectively. Non-nociceptive environmental stress at D10 showed analgesia during stress in K1 (Dunnett, P0.05). Poststress area of hyperalgesia showed that I group developed greater hyperalgesia after NNES than ISSR and IMSR did (Mann-Whitney, P0.05). In experiment 2 in the FIMSR group, NT was significantly higher at postoperative D1 and D2 (Dunnett, P0.05), but no difference was shown from D3 to D10 (Dunnett, P0.05). Hyperalgesic indices calculated for FI and FIMSR groups after NNES at D10 did no show any significant difference (Dunnett, P0.05).Perioperative use of long-lasting RA reduced both acute postoperative hyperalgesia and the development of long-term pain vulnerability. However, high doses of fentanyl for intraoperative analgesia induce central sensitization that cannot be reversed by using long-lasting RA.

Background and Objectives The duration of nerve block is longer in streptozotocin (STZ)–induced diabetic rats for all local anesthetics (with and without adjuvants) compared with normal rats. Perioperative glycemic control is currently practiced to reduce adverse events in many at-risk patients, especially in diabetic patients, to prevent neuropathy, poor wound healing, and greater incidence of infection. The aim of this study was to investigate in diabetic rats the importance of glycemic control before peripheral nerve block. Methods To induce diabetes, rats were intravenously injected with a single dose of 50 mg/kg STZ to destroy pancreatic beta cells. Tactile allodynia in response to von Frey filament stimulation of the plantar hind paws was used as the criterion for diabetic neuropathy. Diabetic rats were randomly divided into experimental treatment groups. The continuous glycemic control experiment compared: 3 U/d insulin implant for 14 days, 1.5 U/d insulin implant for 14 days, and placebo treatment. The acute glycemic control experiment compared a single 6U Human Insulin Isophane Suspension (NPH) injection and placebo treatment. Nondiabetic rats received placebo implants or injections. Following treatment, 0.1 mL of 1% lidocaine hydrochloride with 5 μg/mL epinephrine hydrochloride was injected into the left sciatic notch. Animals were then reevaluated at 10-minute intervals for the absence or presence of sensory and motor response. Results All STZ-injected rats had blood glucose levels greater than 350 mg/dL and tactile allodynia. After insulin implants or injections, diabetic rats had much lower blood glucose levels than diabetic rats with placebo treatment. With both 3 and 1.5 U/d continuous glycemic control, the local anesthetic solution produced a shorter duration of sensory and motor nerve block in insulin-treated diabetic rats compared with placebo-treated diabetic rats, and shorter duration was similar to nondiabetic rats. With 6 U acute glycemic control in diabetic rats, there was no reduction in nerve block duration compared with placebo-treated diabetic rats. Conclusions With continuous glycemic control in diabetic rats, the duration of sensory and motor nerve block was about 40 minutes shorter than that in the untreated diabetic rats and similar to that of normal rats. However, acute glycemic control did not affect nerve block duration, suggesting that this neuropathy cannot be rapidly reversed.

Background: This prospective, randomized, observer-blinded trial compared a subepineural sciatic injection at the neural bifurcation (SUB group) and separate postbifurcation injections around the tibial and peroneal nerves. Methods: Ultrasound-guided posterior popliteal sciatic nerve block was carried out in 50 patients. In the group that had separate postbifurcation injections around the tibial and peroneal nerves, the volume of local anesthetic (LA) (30 mL of lidocaine 1%-bupivacaine 0.25%-epinephrine 5 μg/mL) was divided equally between the tibial and peroneal nerves. In the SUB group, the 2 divisions were identified exactly at the neural bifurcation. In this location, both nerves can still be found inside a common epineural sheath. The entire volume of LA was injected between the 2 branches, inside the common sheath. A blinded observer recorded the success rate (complete sensory block at 30 mins) and onset time. The performance time, number of needle passes, and adverse events were also recorded. Total anesthesia-related time was defined as the sum of performance and onset times. Results: Compared with targeted injections around the tibial and peroneal divisions, a subepineural injection resulted in a higher success rate (84% vs 56%; P = 0.032) as well as improved efficiency (decreased performance/onset/total anesthesia-related times and fewer needle passes; all P ≤ 0.028). In the SUB group, we observed no instance of neural swelling. In 3 subjects randomized to separate injections, sonographic swelling of the tibial nerve occurred after the injection of 2 mL of LA. The needle was carefully withdrawn, and the injection completed uneventfully. In 45 patients, follow-up 1 week after the surgery revealed no sensory or motor deficit. Five subjects were lost to follow-up. Conclusions: Compared with separate injections around the tibial and peroneal divisions, a single subepineural injection at the neural bifurcation provides a higher success rate and requires shorter performance, onset, and total anesthesia-related times. Further studies are required to validate the safety of the subepineural technique.

Background: Ultrasound (US) guidance, in some instances, can increase the success rate and reduce the onset and procedure times for peripheral nerve blockade compared with traditional nerve localization techniques. The presumptive mechanism for these benefits is the ability to accurately inject local anesthetic circumferentially around the target nerve. We aimed to determine whether ensuring circumferential spread of local anesthetic is advantageous for US-guided popliteal sciatic nerve block. Methods: Sixty-four adult patients undergoing US-guided popliteal sciatic block for elective foot and ankle surgery were randomly assigned to 1 of 2 groups, circumferential or single-location injection. Using a short-axis nerve view and out-of-plane needle approach, the needle tip was advanced to the posterior external surface of the sciatic nerve. A 30-mL local anesthetic admixture (1:1 lidocaine 2%/bupivacaine 0.5% with 1:200,000 epinephrine) was injected either entirely at this location (single location) or incrementally at multiple locations to ensure circumferential spread around the sciatic nerve (circumferential). Sensory and motor functions were assessed by a blinded observer at predetermined intervals. The primary outcome was sensory block defined as loss of sensation to pinprick in the distribution of both tibial and common peroneal nerves at 30 mins after injection. Results: Sensory block was achieved in 94% of patients in the circumferential injection group compared with 69% in the single-location injection group (P = 0.010). There were no differences detected in block performance time, pain during block performance, or block-related complications between groups. Conclusions Ultrasound-guided circumferential injection of local anesthetic around the sciatic nerve at the popliteal fossa can improve the rate of sensory block without an increase in block procedure time or block-related complications compared with a single-location injection technique.

Background and Objectives: Continuous sciatic nerve blockade at the popliteal level effectively alleviates postoperative pain after major foot and ankle surgery. No randomized controlled trials have previously compared the success rate of continuous sciatic nerve sensory blockade between ultrasound and nerve stimulation guidance. In the current study, we tested the hypothesis that ultrasound-guided catheter placement improves the success rate of continuous sciatic nerve sensory blockade compared with catheter placement with nerve stimulation guidance. Methods: After research ethics committee approval and informed consent, 100 patients scheduled for elective major foot and ankle surgery were randomly allocated to popliteal catheter placement either with ultrasound or nerve stimulation guidance. The primary outcome was the success rate of sensory block the first 48 postoperative hours. Successful sensory blockade was defined as sensory loss in both the tibial and common peroneal nerve territories at 1, 6, 24, and 48 hrs postoperatively. Results: The ultrasound group had significantly higher success rate of sensory block compared with the nerve stimulation group (94% versus 79%, P = 0.03). Ultrasound compared with nerve stimulation guidance also entails reduced morphine consumption (median of 18 mg [range, 0-159 mg] versus 34 mg [range, 0-152 mg], respectively, P = 0.02), fewer needle passes (median of 1 [range, 1-6] versus 2 [range, 1-10], respectively, P = 0.0005), and greater patient satisfaction (median numeric rating scale 9 [range, 5-10] versus 8 [range, 3-10)] respectively, P = 0.0006) during catheter placement. Conclusion: Ultrasound guidance used for sciatic catheter placement improves the success rate of sensory block, number of needle passes, patient satisfaction during catheter placement, and morphine consumption compared with nerve stimulation guidance.

Background and Objectives: A major concern with the use of continuous peripheral nerve block is the difficulty encountered in placing the catheters close enough to the nerves to accomplish effective analgesia. The aim of this study was to investigate if a self-coiling catheter would remain close to the sciatic nerve once introduced through needles placed under ultrasound guidance and if contrast dye injected through the pigtail catheter made direct contact to the nerves. Methods: First, Tuohy needles were placed anterior to the sciatic nerves under ultrasound guidance (needle-in-plane/nerve in short-axis approach). Next, the self-coiling catheters were blindly introduced through the needles. A total of 40 catheters were placed; 2 per sciatic nerve in the right and left legs of 10 human cadavers. To detect the exact catheter location, computer tomographic imaging of the legs was performed. Finally, the spread of injected contrast dye in relation to the nerves was assessed by magnetic resonance imaging. Results: There was direct contact of the coil with the nerve in 37 cases. In the remaining cases, the shortest distances from the coil to the nerves were 5, 6, and 7 mm. In all but 1 case, the contrast dye was directly in contact with the nerves. The median circumferential covering of the nerve by contrast dye was 50% (25-interquartile range of 40%). Conclusions: By using self-coiling catheters, it is possible to blindly introduce the catheter through needles placed under ultrasound guidance with a low risk of catheter misplacement away from the targeted nerves.

Background and Objectives: The neuropeptide nocistatin has a variety of effects on nociception and other central nervous system functions. It has shown to exert diverging effects on nociceptive behavior in various experimental pain models depending on the dose administered. The inhibitory effect of spinal nocistatin on the release of glycine and γ-aminobutyric acid is thought to be responsible for pronociceptive effects, whereas the antinociceptive action of nocistatin can be attributed to diminished glycine-dependent N-methyl-d-aspartate receptor activation. So far, nocistatin has only been investigated in experimental models of already established pain and has been injected as a bolus. Methods: In the present study, we investigated the effects of continuous intrathecal administration of nocistatin on the development of mechanical allodynia in the chronic constriction injury model of neuropathic pain in rats. The spinal infusion via intrathecal catheters connected to osmotic minipumps was started immediately after the surgical procedure and lasted 24 hrs. The development of mechanical allodynia was assessed with von Frey-type filaments for 2 weeks after chronic constriction injury. Results: Despite a wide range of doses used, the continuous spinal application of nocistatin had no significant effect on the development of pathological nociceptive behavior at any time point, that is, mechanical allodynia developed equally in all groups in the injured paw, whereas nociceptive behavior was unchanged in comparison with baseline values in the uninjured paw in all groups. Conclusions: Because nocistatin has well-documented effects on established pathological pain, it is conceivable that its effect on nociception is only effective when spinal circuitry is pathologically altered.

Background and Objectives The lateral and anterior approaches for proximal sciatic nerve (SN) block can be used in patients lying supine. We assume that the posterior femoral cutaneous nerve (PFCN) is simultaneously blocked more often via the lateral approach than via the anterior approach, given the proximity of these 2 nerves at the injection level. However, locating the SN is difficult when using the original landmark-based lateral approach. We have introduced ultrasound guidance to alleviate the technical difficulty of the lateral approach and tested the hypothesis that an ultrasound-guided lateral approach would achieve PFCN block more often than the ultrasound-guided anterior approach for SN block. Methods Forty consecutive patients undergoing knee surgery were randomly allocated to receive an SN block using an ultrasound-guided lateral or anterior approach. The primary outcome was the frequency of PFCN block 30 minutes after SN block. Secondary outcomes included the frequency of SN block, nerve depth, needle depth, and time taken to perform the block. We also assessed the spread of injectate by the lateral approach in 4 cadaveric legs. Results The frequency of PFCN block 30 minutes after SN block was higher with the lateral approach than with the anterior approach (60% vs 15%, P = 0.008). The frequency of SN block was comparable between the groups. Dye reached the PFCN in all cadaveric specimens. Conclusions The ultrasound-guided lateral approach for proximal SN block can be performed as successfully as the anterior approach and provides PFCN block more often than the anterior approach. Clinical Trial Registration This study was registered at UMIN Clinical Trials Registry, identifier UMIN000026748.

Although intravenous lipid emulsion has been proved a powerful antidote for local anesthetic toxicity, there are few pharmacokinetic data on using lipid infusion as a pretreatment for other clinical applications. We assessed the influence of lipid pretreatment on the pharmacodynamics and pharmacokinetics of levobupivacaine.Altogether, 12 patients undergoing below-knee surgery for a fracture were randomly assigned to 2 groups (6 patients per group): pretreatment with 1.5 mL/kg lipid infusion (lipid group) or saline infusion (control subjects) followed by complete femoral and sciatic nerve block with 0.375% levobupivacaine (2.5 mg/kg). Total and free (non-protein bound) plasma levobupivacaine concentrations and triglycerides in the lipid group were determined.Results were given as means ± SD. Total and free maximum plasma levobupivacaine concentrations were lower in the lipid group than in control subjects (865 ± 98 vs 1145 ± 177 μg/L and 56.8 ± 7.5 vs 78.2 ± 13.7 μg/L, respectively; P0.01). Apparent volume of distribution and clearance were higher in the lipid group than in control subjects (211 ± 35 vs 170 ± 21 L and 35.1 ± 8.0 vs 25.8 ± 2.6 L/h, respectively; P0.05). Triglyceride level was significantly higher at the end of lipid infusion than baseline values (7.59 ± 1.32 vs 1.34 ± 0.39 mmol/L; P0.01).Lipid pretreatment increased the apparent volume of distribution and clearance and decreased the maximum total and free levobupivacaine concentrations, thus offering a reasonable explanation for the effects of lipids on local anesthesia-related toxicity in humans. Rapid lipid infusion induced hypertriglyceridemia without other apparent risks in this study.This study was registered at the Chinese Clinical Trial Registry, identifier ChiCTR-TRC-14005203.

Background and Objectives: When the conventional lateral popliteal sciatic nerve (SN) block is performed, the needle angle required to localize and the level of the SN bifurcation are highly variable. The aim of our magnetic resonance imaging (MRI) study was to determine the most common range of needle-insertion angles and the relationship between skin-to-femur distance and angle. We also evaluated the variability of the SN bifurcation level and the relationship between patient height and nerve bifurcation level. Methods: Using 289 thigh MRIs to simulate a lateral approach in the supine position, we measured and analyzed with simple linear regressions the level of SN bifurcation, the skin-to-femur and SN-to-femur distances, and the angle at which the needle must be directed posteriorly to intersect the SN at 9 cm proximal to the lateral joint line. Results: The mean insertion angle was 30 (SD, 8) degrees. In 95% of cases, angles ranged from 15 to 45 degrees, and the larger the thigh, the smaller the angle. The SN divided at a mean distance of 7.5 (SD, 1.6) cm (range, 1.5-12.8 cm) proximal to the lateral joint line. In 93% of cases, the bifurcation level was 10 cm or less. Conclusions: Our simulated lateral popliteal SN block on MRIs shows a 15- to 45-degree range of needle-insertion angles. As the skin-to-femur distance was greater than 4.5 cm, the angles were progressively smaller than 30 degrees. Although this was an MRI study, it does provide some evidence that indicates the conventional clinically recommended 25- to 30-degree-angle ranges may need to be reevaluated. Needle insertion of 10 cm or greater proximal to the popliteal crease may increase the chance of placement at or proximal to the SN bifurcation.

Background and Objectives: Popliteal sciatic nerve block (SNB) in combination with saphenous nerve block provides anesthesia and analgesia for foot and ankle surgeries. Landmark-based and image-guided techniques, to date, aim at blocking the sciatic nerve proximal to its bifurcation. Sciatic nerve block is usually associated with a long onset time (30-60 mins). We hypothesized that SNB distal to its bifurcation (blocking its 2 main branches tibial and common peroneal nerves separately) is associated with a shorter onset time than blockade proximal to its bifurcation. Methods: Fifty patients scheduled for major elective foot or ankle surgery were randomly allocated to receive ultrasound-guided SNB 5 cm proximal to (group P) or 3 cm distal to (group D) its bifurcation in the popliteal fossa. Thirty milliliters of a standardized local anesthetic solution of equal volumes of 2% lidocaine and 0.5% bupivacaine with 1:200,000 epinephrine was used. Sensory and motor assessments were performed every 5 mins by a blinded observer until complete sensory and motor blockade developed in both tibial and common peroneal nerve territories. Results: All patients in both groups developed a complete block. Patients in group D presented a 30% shorter onset of both sensory (21.4 [SD, 9.9] vs 31.4 [SD, 13.9] mins) (P = 0.005) and motor block (21.5 [SD, 11.3] vs 32.4 [SD, 14.9] mins) (P = 0.006) than patients in group P. Procedure time, procedure-related discomfort, and patient satisfaction were similar in both groups. Conclusions: Our data suggest that popliteal SNB distal to the bifurcation has a shorter onset time than SNB proximal to its bifurcation, and therefore, it may be a good option when a fast onset for a surgical block is required.

Astrocyte activation has been implicated in the pathogenesis of neuropathic pain, but the involvement of kindlin-1 in astrocyte activation and neuropathic pain has not yet been illustrated. Using a chronic constriction injury (CCI) rat model of neuropathic pain, we investigated the expression levels of kindlin-1 during neuropathic pain and the influences of kindlin-1 on regulating pain sensitivity.Neuropathic pain was induced in rats by CCI of the sciatic nerve. Rats were randomly assigned to 4 groups: sham operation, CCI, CCI + kindlin-1 short hairpin RNA (shRNA), and CCI + kindlin-1 groups. Animals in the CCI + kindling-1 shRNA and CCI + kindlin-1 groups were given kindlin-1 shRNA or kindlin-1 virus infection to reduce or overexpress kindlin-1, respectively. Kindlin-1 expression was persistently increased in rats 10 days after CCI. A large proportion of glial fibrillary acidic protein (GFAP)-positive astrocytes expressed kindlin-1 in spinal cord tissues of rats after CCI.Compared with the sham operation group, CCI animals exhibited increased GFAP expression and GFAP-positive astrocytes in the spinal cord. Down-regulation of kindlin-1 reduced the up-regulation of GFAP in the spinal cord, whereas overexpression of kindlin-1 promoted elevation of GFAP levels. Kindlin-1 silencing elevated the mechanical and thermal pain thresholds of CCI rats (P0.05). However, overexpression of kindlin-1 aggravated CCI-induced pain sensitivity.Kindlin-1 may regulate pain sensitivity by affecting activated astrocytes in the spinal cord. Inhibition of kindlin-1 may provide a novel paradigm for the management of neuropathic pain.

Background and Objectives: Stimulating catheters provide feedback regarding the location of the catheter tip in relation to the target nerve or plexus. There is debate concerning whether stimulating catheters may reduce the failure rate of postoperative analgesia or whether they may enhance functional recovery by providing superior and more reliable postoperative analgesia. Methods: Studies comparing the effect of stimulating versus nonstimulating catheters for postoperative analgesia were systematically and independently searched by 2 authors. Results: Eleven randomized controlled studies could be included in this review. One trial was performed in volunteers; the others were clinical trials in patients. Five trials were performed in patients scheduled for a femoral nerve catheter, 4 for a distal sciatic nerve catheter, 1 in patients receiving an interscalene nerve catheter, and 1 in patients with an infraclavicular brachial plexus block. A standard quantitative analysis was deemed inappropriate because of considerable heterogeneity regarding the investigated outcome parameters. A semiquantitative review revealed that efficacy (judged by reduction in the need for rescue analgesics, complete surgery block, or median effective local anesthetic volume blocking the nerve) suggests improvement in stimulating catheters compared with nonstimulating catheters. Patient satisfaction as well as functional recovery was poorly investigated, so no conclusions could be drawn. Conclusions: Published reports of randomized controlled trials provide evidence for a better analgesic effect from stimulating catheters. Future trials should be conducted in a standardized manner with uniform reporting of outcomes, which may facilitate future quantitative analysis.

Contains fulltext : 87659.pdf (Publisher’s version ) (Closed access) BACKGROUND AND OBJECTIVES: Efficient identification of the sciatic nerve (SN) requires a thorough knowledge of its topography in relation to the surrounding structures. Anatomic cross sections in similar oblique planes as observed during SN ultrasonography are lacking. A survey of sonoanatomy matched with ultrasound views of the major SN block sites will be helpful in pattern recognition, especially when combined with images that show the internal architecture of the nerve. METHODS: From 1 cadaver, consecutive parts of the upper leg corresponding to the 4 major blocks sites were sectioned and deeply frozen. Using cryomicrotomy, consecutive transverse sections were acquired and photographed at 78-microm intervals, along with histologic sections at 5-mm intervals. Multiplanar reformatting was done to reconstruct the optimal planes for an accurate comparison of ultrasonography and gross anatomy. The anatomic and histologic images were matched with ultrasound images that were obtained from 2 healthy volunteers. RESULTS: By simulating the exact position and angulation as in the ultrasonographic images, detailed anatomic overviews of SN and adjacent structures were reconstructed in the gluteal, subgluteal, midfemoral, and popliteal regions. Throughout its trajectory, SN contains numerous fascicles with connective and adipose tissues. CONCLUSIONS: In this study, we provide an optimal matching between histology, anatomic cross sections, and short-axis ultrasound images of SN. Reconstructing ultrasonographic planes with this high-resolution digitized anatomy not only enables an overview but also shows detailed views of the architecture of internal SN. The undulating course of the nerve fascicles within SN may explain its varying echogenic appearance during probe manipulation.