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Background and Objectives Local anesthetics (LAs) are widely known for inhibition of voltage-gated sodium channels underlying their antiarrhythmic and antinociceptive effects. However, LAs have significant immunomodulatory properties and were shown to affect human neutrophil functions independent of sodium-channel blockade. Previous studies suggest a highly selective interaction between LAs and the α-subunit of G protein–coupled receptors of the Gq/G11 family as underlying mechanism. Providing a detailed structure function analysis, this study aimed to determine the active parts within the LA molecule responsible for the effects on human neutrophil priming. Methods Human neutrophils were incubated with structurally different LAs for 60 minutes, followed by priming and activation using either platelet-activating factor or lysophosphatidic acid and N-formyl-methionyl-L-leucyl-L-phenylalanine. Superoxide anion generation was determined, using the cytochrome c reduction assay. Results Differences in priming inhibition of human neutrophils between LAs were smaller than expected, although significant. Ester-linked LAs blocked priming responses more effectively than did amide LAs. Furthermore, the inhibitory potency of LAs on priming decreased with an increase of their respective octanol-buffer coefficient, and inhibition did not correlate with sodium-channel–blocking potency. Charge was not crucially required for priming inhibition, yet it played a role in effect size. Conclusions Local anesthetics significantly attenuated Gαq-protein–mediated neutrophil priming. The most potent inhibition was achieved by ester compounds, inversely correlated with their octanol-buffer coefficient, and enhanced by permanent charges within the LA molecule. No correlation to their potency of blocking sodium channels was found.

Background and Objectives Use of ultrasound-guided regional anesthesia (UGRA) requires considerable training. An embedded electronic tutorial as an element of an ultrasound machine may help to identify sonoanatomy for novices. Therefore, we investigated whether an electronic tutorial could improve accuracy or speed of performance in identifying anatomical structures. Methods Thirty-five novices in UGRA participated in a workshop on brachial plexus sonoanatomy. Following a lecture and training in handling of ultrasound machines and hand-eye coordination, participants were randomized in either group S, using a standard ultrasound machine, or group T, using the same type of machine with an onboard electronic tutorial. Each participant had to identify 27 anatomical structures from the brachial plexus of a volunteer. A correctly identified structure scored 1 point. An experienced observer noted scores and time required. Scores ± SD (in %) and times ± SD (in seconds) were compared between groups by analyses of independent-samples t test and analysis of variance. Influence of anesthesia experience was determined by multivariate analyses. Results Group T scored significantly higher (16.8 ± 3.6 [62%] vs 13.4 ± 4.4 [50%], P = 0.018), whereas time required was longer (1053 ± 244 vs 740 ± 244 seconds, P = 0.001). Multivariate analysis revealed that experience had no influence on scores or time required. Examination of structures took more time in the beginning than at the end in group T. Conclusions An electronic tutorial can help novices in UGRA identify anatomical structures. A significant increase in correct identifications was gained at the expense of significantly longer time required for this process. Increased time required may partly be related to unfamiliarity with the tutorial.

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.

Background: Neurotoxic properties of local anesthetics can rarely lead to irreversible neuronal damage as in cauda equina syndrome. Clinically, local anesthetics are often combined with adjuvants to improve or prolong the anesthetic effect, whereas the impact of such adjuvants on lidocaine-induced apoptosis is unclear. Therefore, we investigated the influence of different adjuvants on the neurotoxicity of lidocaine. Methods: Human neuroblastoma cells and primary rat astrocytes were incubated for 24 hrs with lidocaine at a toxic concentration alone and in combination with morphine, sufentanil, clonidine, epinephrine, neostigmine, ketamine, and midazolam. Subsequently, the rates of cell death and early apoptosis were measured by flow cytometry in neuroblastoma cells, whereas astrocyte viability was analyzed by mitochondrial activity assay. In addition, isobolograms were calculated to describe the additive effects of lidocaine with ketamine or midazolam, respectively. Results: Coadministration of lidocaine with sufentanil, clonidine, epinephrine, and neostigmine did not alter the rates of cell death compared with cells treated with lidocaine alone. Morphine improved the viability of astrocytes only at concentrations beyond those occurring clinically. In contrast, coincubation of lidocaine with ketamine or midazolam led to significantly increased rates of cell death. The combined toxicity of ketamine and lidocaine was additive, whereas the combined toxicity of midazolam and lidocaine was subadditive. Conclusions: Sufentanil, clonidine, epinephrine, and neostigmine do not influence the neurotoxicity of lidocaine in vitro. Morphine may have some cytoprotective effect at concentrations greater than those seen intrathecally in humans. In contrast, ketamine and midazolam increase the neurotoxicity of lidocaine in vitro, presumably by additive induction of mitochondrial apoptosis.

Background and Objectives: In neuraxial anesthesia, increase of skin temperature is an early sign of successful block. Yet, during peripheral nerve block of the lower extremity, increase in skin temperature is a highly sensitive, but late sign of a successful block. We hypothesized that after interscalene brachial plexus block, a rise in skin temperature follows impairment of sensation during successful nerve block and occurs only distally, as observed in the lower extremity. Methods: in the present study, we prospectively evaluated the changes in skin temperature after interscalene brachial plexus blockade in 45 patients scheduled for elective shoulder surgery. We assessed pinprick and cold sensation as well as skin temperature at sites of the skin innervated by the median, ulnar, radial, axillary and musculocutaneous nerve. Results: At the skin areas innervated by the axillary and musculocutaneous nerve, skin temperature did not increase after successful block. At the distal sites, innervated by the median, ulnar, and radial nerve, skin temperature increased significantly (1.9-2.1 degrees C within 30 min) after successful block while it did not after failed nerve block or on the contralateral side. in these areas attenuation of skin sensation preceded a measurable rise in skin temperature ( >= 1 degrees C) in 56.3% of nerve blocks, occurred at the same time in 35.2%, and in 8.5% the temperature rise occurred first. Conclusions: Assessment of skin temperature cannot predict the success of an interscalene brachial plexus block of the axillary and musculocutaneous nerve. Distally, the increase of skin temperature has a high sensitivity and specificity but occurs later than the loss of sensory and motor functions. Therefore, the measurement of skin temperature during interscalene blockade is of limited clinical value

BACKGROUND AND OBJECTIVES: Skin-temperature increase is a reliable but late indicator of success during regional-anesthesia techniques. The goal of this study is to determine the distribution of skin-temperature changes during different regional techniques. Does skin temperature increase in the whole area innervated by the blocked neural structures or only in certain regions within this area with the capability to react preferentially to sympathetic block (i.e., vessel-rich skin)? Although onset time may vary between different regional-anesthetic techniques, we hypothesized that the distribution of skin warming is equal. METHODS: Skin temperature was assessed continuously by infrared thermography in 24 patients who received either combined femoral-nerve and sciatic-nerve block, epidural anesthesia, or spinal anesthesia. RESULTS: Apart from differences in time of onset, no differential spatial distribution of skin-temperature changes could be detected. The earliest and greatest rise of skin temperature occurred at the great toe (10.6 degrees C +/- 0.4 degrees C), became smaller proximally, and was negligible above the ankles, irrespective of the type and extent of block. Video-thermography revealed that cold blood flows through subcutaneous veins immediately after onset of sympathetic block and initially decreases skin temperature (0.6 degrees C +/- 0.3 degrees C) during onset of spinal anesthesia. CONCLUSION: Irrespective of the applied regional-anesthetic technique, skin-temperature changes are more pronounced distally. Thermography prevents false measurements of skin temperature above subcutaneous veins and displays flow of cold blood as the mechanism of initial skin-temperature drop after regional anesthesia. Measurements of skin-temperature increase cannot be used to evaluate the extent of analgesia or sympathetic block

Objective: Stimulating catheters have been introduced into clinical practice to confirm perineural localization of the catheters. The muscular twitch induced over the catheter may be used to evaluate nerve function intraoperatively. Therefore, the function of the sciatic nerve was evaluated during major cancer surgery of the femur. Case Report: A 7-year-old boy (29 kg) was scheduled for hip rotationplasty for resection of an osteosarcoma of the left femur under general anesthesia and postoperative pain therapy with an epidural stimulating catheter. In hip rotationplasty the femur is resected, the lower limb and foot are rotated 180 degrees and the tibia plateau is attached to the pelvic acetabulum to form a new hip joint. During preparation of the left thigh and the sciatic nerve, motor responses to stimulation of the catheter were preserved, but the stimulation threshold increased. After vascular anastomosis the foot remained cold, therefore ropivacaine was applied epidurally and subsequently a warming of the foot was observed. At the end of the operation, the patient was free of pain, a good capillary pulse of the leg was observed, and the patient was able to move the foot and toes of the rotated leg. Conclusions: The use of epidural stimulating catheters as a tool to monitor nerve function is a novel and simple procedure to monitor nerve function intraoperatively and to enable good postoperative pain control.