Pentobarbital may protect against neurogenic inflammation after surgery via inhibition of substance P release from peripheral nerves of rats.

The inflammatory response related to surgery is considered surgical inflammation. Most anesthetic agents directly or indirectly suppress the immune response. However, the intravenous anesthetics pentobarbital and ketamine were reported to inhibit the lipopolysaccharide-induced inflammatory response such as cytokines formation. Neurogenic inflammation is inflammation originating from the local release of inflammatory mediators, such as substance P (SP), by primary afferent neurons after noxious stimuli like surgery. Thus, in this study, we examined whether pentobarbital and ketamine suppress SP release from cultured dorsal root ganglion (DRG) neurons. DRG cells were dissected from male Wistar rats. Released SP was measured by radioimmunoassay. We demonstrated that higher concentrations of pentobarbital (100-1,000 µM) significantly inhibited capsaicin (100 nM)-induced, but not high K+ (50 mM)-induced, SP release from DRG cells, although a high concentration of ketamine (1 mM) did not. This study revealed that pentobarbital functions between the activation of vanilloid receptor subtype 1 (TRPV1) receptors, to which capsaicin selectively binds, and the opening of voltage-operated Ca2+ channels (VOCC) in the nerve endings. Therefore, the anti-inflammatory action of pentobarbital is mediated through different mechanisms than those of ketamine. Thus, the inhibitory effect of pentobarbital on SP release from peripheral terminals may protect against neurogenic inflammation after surgery.

Therapeutic Potential of Complementary and Alternative Medicines in Peripheral Nerve Regeneration: A Systematic Review.

Despite the progressive advances, current standards of treatments for peripheral nerve injury do not guarantee complete recovery. Thus, alternative therapeutic interventions should be considered. Complementary and alternative medicines (CAMs) are widely explored for their therapeutic value, but their potential use in peripheral nerve regeneration is underappreciated. The present systematic review, designed according to guidelines of Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols, aims to present and discuss the current literature on the neuroregenerative potential of CAMs, focusing on plants or herbs, mushrooms, decoctions, and their respective natural products. The available literature on CAMs associated with peripheral nerve regeneration published up to 2020 were retrieved from PubMed, Scopus, and Web of Science. According to current literature, the neuroregenerative potential of Achyranthes bidentata, Astragalus membranaceus, Curcuma longa, Panax ginseng, and Hericium erinaceus are the most widely studied. Various CAMs enhanced proliferation and migration of Schwann cells in vitro, primarily through activation of MAPK pathway and FGF-2 signaling, respectively. Animal studies demonstrated the ability of CAMs to promote peripheral nerve regeneration and functional recovery, which are partially associated with modulations of neurotrophic factors, pro-inflammatory cytokines, and anti-apoptotic signaling. This systematic review provides evidence for the potential use of CAMs in the management of peripheral nerve injury.

The Role of Dietary Nutrients in Peripheral Nerve Regeneration.

Peripheral nerves are highly susceptible to injuries induced from everyday activities such as falling or work and sport accidents as well as more severe incidents such as car and motorcycle accidents. Many efforts have been made to improve nerve regeneration, but a satisfactory outcome is still unachieved, highlighting the need for easy to apply supportive strategies for stimulating nerve growth and functional recovery. Recent focus has been made on the effect of the consumed diet and its relation to healthy and well-functioning body systems. Normally, a balanced, healthy daily diet should provide our body with all the needed nutritional elements for maintaining correct function. The health of the central and peripheral nervous system is largely dependent on balanced nutrients supply. While already addressed in many reviews with different focus, we comprehensively review here the possible role of different nutrients in maintaining a healthy peripheral nervous system and their possible role in supporting the process of peripheral nerve regeneration. In fact, many dietary supplements have already demonstrated an important role in peripheral nerve development and regeneration; thus, a tailored dietary plan supplied to a patient following nerve injury could play a non-negotiable role in accelerating and promoting the process of nerve regeneration.

Prior perineural or neonatal treatment with capsaicin does not alter the development of spinal microgliosis induced by peripheral nerve injury.

Peripheral nerve injury is associated with spinal microgliosis which plays a pivotal role in the development of neuropathic pain behavior. Several agents of primary afferent origin causing the microglial reaction have been identified, but the type(s) of primary afferents that release these mediators are still unclear. In this study, specific labeling of C-fiber spinal afferents by lectin histochemistry and selective chemodenervation by capsaicin were applied to identify the type(s) of primary afferents involved in the microglial response. Comparative quantitative morphometric evaluation of the microglial reaction in central projection territories of intact and injured peripheral nerves in the superficial (laminae I and II) and deep (laminae III and IV) spinal dorsal horn revealed a significant, about three-fold increase in microglial density after transection of the sciatic or the saphenous nerve. Prior perineural treatment of these nerves with capsaicin, resulting in a selective defunctionalization of C-fiber afferent fibers failed to affect spinal microgliosis. Similarly, peripheral nerve injury-induced increase in microglial density was unaffected in rats treated neonatally with capsaicin known to result in a near-total loss of C-fiber dorsal root fibers. Perineural treatment with capsaicin per se did not evoke a significant increase in microglial density. These observations indicate that injury-induced spinal microgliosis may be attributed to phenotypic changes in injured myelinated primary afferent neurons, whereas the contribution of C-fiber primary sensory neurons to this neuroimmune response is negligible. Spinal myelinated primary afferents may play a hitherto unrecognized role in regulation of neuroimmune and perisynaptic microenvironments of the spinal dorsal horn.

Discovery and biological characterization of a novel scaffold for potent inhibitors of peripheral serotonin synthesis.

Aim: Tryptophan hydroxylase 1 (TPH1) catalyzes serotonin synthesis in peripheral tissues. Selective TPH1 inhibitors may be useful for treating disorders related to serotonin dysregulation. Results & methodology: Screening using a thermal shift assay for TPH1 binders yielded Compound 1 (2-(4-methylphenyl)-1,2-benzisothiazol-3(2H)-one), which showed high potency (50% inhibition at 98 ± 30 nM) and selectivity for inhibiting TPH over related aromatic amino acid hydroxylases in enzyme activity assays. Structure-activity relationships studies revealed several analogs of 1 showing comparable potency. Kinetic studies suggested a noncompetitive mode of action of 1, with regards to tryptophan and tetrahydrobiopterin. Computational docking studies and live cell assays were also performed. Conclusion: This TPH1 inhibitor scaffold may be useful for developing new therapeutics for treating elevated peripheral serotonin.

Breast surgery and peripheral blocks. Is it worth it?

PURPOSE OF REVIEW: The objective of this review is to identify the potential of peripheral nerve blocks established over the last years for perioperative pain management in breast surgery. These new blocks will be discussed with respect to their clinical effect and necessity. RECENT FINDINGS: After case reports and cadaver studies for the Pecs block and its variations sufficient clinical data from randomized controlled trial (RCT) and meta-analyses exist now. The modified Pecs block or Pecs II leads to a reduction of postoperative 24-h opioid consumption. The recently invented Erector spine block addresses the intercostal nerves. The benefits in analgesia of this approach were tested in few RCTs and showed superiority to the control group in terms of requested postoperative morphine. Most studies showed low intraoperative opioid doses and no study more than low to moderate postoperative pain scores. SUMMARY: Taking the pain levels after breast surgery into account, the request of additional nerve blocks has to be pondered against the potential risks and resource requirement. To reduce or avoid intraoperative or postoperative opioids, an ultrasound-guided Pecs II block proves to be the best option for perioperative pain relief.

A physiological dose of oral vitamin B-12 improves hematological, biochemical-metabolic indices and peripheral nerve function in B-12 deficient Indian adolescent women.

BACKGROUND: Vitamin B-12 deficiency is often considered synonymous with pernicious anemia, a rare condition in which severe malabsorption of the vitamin requires high-dose parenteral treatment. In developing countries such as India, inadequate dietary intake of B-12 due to socio-cultural factors leads to widely prevalent asymptomatic low B-12 status. In this scenario, lower doses of oral B-12 may be effective, safer and more affordable. OBJECTIVE: To examine the effects of oral B-12 treatment at physiological doses on hematological and biochemical indices and peripheral nerve function in B-12 deficient rural Indian adolescent women. METHODS: Thirty-nine women with B-12 deficiency who were excluded from a community based B-12 supplementation trial (Pune Rural Intervention in Young Adolescents (PRIYA)) received oral B-12 2µg/day, either alone (n = 19) or with multiple micronutrients (UNIMAPP formula + 20gm milk powder, n = 20) for 11 months. Hematological indices, nutrients (B-12, folate), metabolites (homocysteine) and peripheral nerve function (SUDOSCAN, Impetomedical, Paris and sensory nerve conduction velocity (NCV) of median and sural nerves) were assessed at baseline and after 11 months of B-12 treatment. RESULTS: Results were similar in the two treatment allocation groups, which were therefore combined. At baseline, all women had B-12 concentration <100pmol/L, 79% were anemic and 33% had macrocytosis, but none had neuropathy. After 11 months of treatment, B-12 levels increased, while folate did not change. The prevalence of anemia fell to 59% and mean corpuscular volume (MCV) and plasma homocysteine concentrations decreased. Sudomotor nerve function in the feet improved by an average of 14.7%, and sensory conduction velocity in median and sural nerves increased by 16.2% and 29.4% respectively. CONCLUSION: We document clinically beneficial effects of supplementation with a physiological dose of oral B-12 in asymptomatic rural Indian adolescent women with very low B-12 status. These findings support a public health approach to tackle the widely prevalent low B-12 status in young Indians.

Percutaneous peripheral nerve stimulation and other alternatives for perineural catheters for postoperative analgesia.

A perineural catheter with a continuous infusion of local anesthetic is an excellent option for postoperative analgesia; however, its limitations include limited duration of action (i.e., 3-7 days) as well as a risk of infection and dislodgement. Furthermore, these blocks may cause dense sensory and motor blockades that under certain circumstances may not be ideal. There is novel evidence that ultrasound-guided percutaneous peripheral nerve stimulation (pPNS) may serve as an alternative approach free of the limitations associated with peripheral nerve blocks. In this review, we discuss the evidence for pPNS on postoperative acute pain management. Subsequently, we briefly discuss additional alternatives to continuous peripheral nerve blocks, including cryoanalgesia and liposomal bupivacaine.

[Background and current use of adjuvants for regional anesthesia : From research to evidence-based patient treatment]. / Hintergrund und aktueller Einsatz von Adjuvanzien für die Regionalanästhesie : Aus der Forschung in die evidenzbasierte Patientenversorgung.

The discovery of the local anaesthetic effect by blocking sodium ion channels was a milestone in anaesthesia but was soon limited by sometimes life-threatening toxic effects of the local anaesthetics. By developing novel local anaesthetics and also by adding so-called adjuvants, attempts have been made to limit these life-threatening events. This article focuses on the historic background and the current state of the use of these adjuvants for regional anaesthesia. Adding epinephrine, clonidine or dexmedetomidine, but only as a single dose, results in a faster onset, longer duration of action and increased intensity of neuronal blockade of regional anaesthesia. The benefits of adding sodium bicarbonate, on the other hand, are relatively minor and, therefore, clinically negligible. Although increasing evidence in the literature suggests an improvement and prolongation of the analgesic effect after axonal administration of opioids, which can also be given continuously, systemic effects are not fully ruled out due to the increased incidence of central side effects. The partial local anaesthetic effects of opioids cannot always be distinguished from opioid receptor-specific effects. Mechanistic studies postulate a functional coupling of opioid receptors in injured rather than in intact peripheral nerves. Recent studies have identified glucocorticoid and mineralocorticoid receptors predominantly on peripheral nociceptive nerve fibers. This is consistent with numerous clinical reports of a marked prolongation of the local anaesthetic effect. In addition to the known genomic effects of steroids that occur via a change in gene expression of pain-sustaining protein structures, faster non-genomic effects are also discussed, which occur via a change in intracellular signaling pathways. In summary, new insights into mechanisms and novel results from clinical trials will help the anaesthesiologist in the decision to use adjuvants for regional anaesthesia which, however, requires to weigh the individual patient's benefits against the risks.

Cardioprotection via the skin: nociceptor-induced conditioning against cardiac MI in the NIC of time.

Timely reperfusion is still the most effective approach to limit infarct size in humans. Yet, despite advances in care and reduction in door-to-balloon times, nearly 25% of patients develop heart failure postmyocardial infarction, with its attendant morbidity and mortality. We previously showed that cardioprotection results from a skin incision through the umbilicus in a murine model of myocardial infarction. In the present study, we show that an electrical stimulus or topical capsaicin applied to the skin in the same region induces significantly reduced infarct size in a murine model. We define this class of phenomena as nociceptor-induced conditioning (NIC) based on the peripheral nerve mechanism of initiation. We show that NIC is effective both as a preconditioning and postconditioning remote stimulus, reducing infarct size by 86% and 80%, respectively. NIC is induced via activation of skin C-fiber nerves. Interestingly, the skin region that activates NIC is limited to the anterior of the T9-T10 vertebral region of the abdomen. Cardioprotection after NIC requires the integrity of the spinal cord from the region of stimulation to the thoracic vertebral region of the origin of the cardiac nerves but does not require that the cord be intact in the cervical region. Thus, we show that NIC is a reflex and not a central nervous system-mediated effect. The mechanism involves bradykinin 2 receptor activity and activation of PKC, specifically, PKC-α. The similarity of the neuroanatomy and conservation of the effectors of cardioprotection supports that NIC may be translatable to humans as a nontraumatic and practical adjunct therapy against ischemic disease. NEW & NOTEWORTHY This study shows that an electrical stimulus to skin sensory nerves elicits a very powerful cardioprotection against myocardial infarction. This stimulus works by a neurogenic mechanism similar to that previously elucidated for remote cardioprotection of trauma. Nociceptor-induced conditioning is equally potent when applied before ischemia or at reperfusion and has great potential clinically.

Saponins of Tribulus terrestris attenuated neuropathic pain induced with vincristine through central and peripheral mechanism.

The study comprises exploring the effects of saponins from Tribulus terrestris (TT) in attenuating the neuropathic pain caused by vincristine (100 µg/ml i.p.) for 10 days (in two 5 day cycles with 2 days pause). Mechanical hyperalgesia and allodynia were assessed by Randall-Sellitto and electronic von Frey tests, respectively. Chemical- induced nociception was assessed by formalin test. Neurophysiological effect of the extract was evaluated by recording sciatic functional index (SFI) on the test days (7, 10, 14, and 21) and sciatic nerve conduction velocity test (SNCV) on the last day. Inflammatory mediators (TNF-α, IL-1ß, and IL-6) in both sciatic nerve and brain and brain neurotransmitters, glutamate and aspartate, were measured to support the behavioral response. The saponins of TT-treated group were found to be effective in the behavioral experiments, implying its activity both centrally and peripherally in attenuating pain. The inflammatory mediators in both sciatic nerve and brain (TNF-α, IL-1ß, and IL-6) were found to be attenuated with TT saponin treatment in comparison to vincristine-treated group, indicating its anti-inflammatory property. The excitatory neurotransmitters, L-glutamic acid and L-aspartic acid, were also found to be attenuated with TT saponins, implying restoration of neuronal damage and synaptic activity caused by high amount of glutamate due to excess TNF-α in brain and reversing the nociceptive threshold lowered due to aspartate. Thus, TT(S) is peripherally and centrally active in lowering the inflammatory mediators, reversing the neuronal damage and increasing the nociceptive threshold caused due to peripheral neuropathy.

Electroacupuncture induces antihyperalgesic effect through endothelin-B receptor in the chronic phase of a mouse model of complex regional pain syndrome type I.

Complex regional pain syndrome (CRPS) is a disorder that involves abnormal inflammation and nerve dysfunction frequently resistant to a broad range of treatments. Peripheral nerve stimulation with electroacupuncture (EA) has been widely used in different clinical conditions to control pain and inflammation; however, the use of EA in the treatment of CRPS is under investigation. In this study, we explore the effects of EA on hyperalgesia and edema induced in an animal model of chronic post-ischemia pain (CPIP model) and the possible involvement of endothelin receptor type B (ETB) in this effect. Female Swiss mice were subjected to 3 h hind paw ischemia/reperfusion CPIP model. EA treatment produced time-dependent inhibition of mechanical and cold hyperalgesia, as well as edema in CPIP mice. Peripheral administration (i.pl.) of BQ-788 (10 nmol), an ETB antagonist, prevented EA-induced antihyperalgesia while intrathecal administration prolonged EA's effect. Additionally, peripheral pre-treatment with sarafotoxin (SRTX S6c, 30 pmol, ETB agonist) increased EA anti-hyperalgesic effect. Furthermore, the expression of peripheral ETB receptors was increased after EA treatments, as measured by western blot. These results may suggest that EA's analgesic effect is synergic with ETB receptor activation in the periphery, as well as central (spinal cord) ETB receptor blockade. These data support the use of EA as a nonpharmacological approach for the management of CRPS-I, in an adjuvant manner to ETB receptor targeting drugs.

Updated Retrospective Single-Center Comparative Analysis of Peripheral Nerve Block Complications Using Landmark Peripheral Nerve Stimulation Versus Ultrasound Guidance as a Primary Means of Nerve Localization.

OBJECTIVES: The purpose of this study was to perform an updated analysis of complications associated with upper and lower extremity peripheral nerve blocks (PNBs) performed with ultrasound (US) guidance versus the landmark approach. METHODS: We conducted a single-center retrospective cohort analysis to compare the incidence of PNB complications between the techniques. The primary outcome was local anesthetic systemic toxicity (LAST), whereas the secondary outcomes included short- and long-term nerve injuries. The current query included cases performed between 2012 and 2015. A combined analysis included data extending to 2006. The Statistical examination relied on the χ2 test. RESULTS: During this 4-year period, we performed 7789 US-guided and 498 landmark-guided blocks with no statistically significant difference in the incidence of nerve injury or LAST between the groups. Our 10-year analysis, however, revealed a significant increase (P < .01) in the rate of LAST with the landmark technique: 7 of 5932 versus 0 of 16,858 cases. The combined data also revealed a significant increase (P < .01) in short-term injuries associated with the landmark approach (30 of 5932 versus 33 of 16,858) but no significant difference in the incidence of long-term injuries. CONCLUSIONS: Our analysis supports a conclusion that the use of US guidance during PNBs leads to a significant reduction in the incidence of LAST, adding to growing evidence from similar investigations. The impact of US on the incidence of nerve injuries remains unclear, considering that the nature of transient deficits is thought to be multifactorial, and the frequency of lasting injuries did not differ significantly in this study.

Protective effects of methanolic extract of Juglans regia L. leaf on streptozotocin-induced diabetic peripheral neuropathy in rats.

BACKGROUND: Oxidative stress has a pivotal role in the pathogenesis and development of diabetic peripheral neuropathy (DPN), the most common and debilitating complications of diabetes mellitus. There is accumulating evidence that Juglans regia L. (GRL) leaf extract, a rich source of phenolic components, has hypoglycemic and antioxidative properties. This study aimed to determine the protective effects of Juglans regia L. leaf extract against streptozotocin-induced diabetic neuropathy in rat. METHODS: The DPN rat model was generated by intraperitoneal injection of a single 55 mg/kg dose of streptozotocin (STZ). A subset of the STZ-induced diabetic rats intragastically administered with GRL leaf extract (200 mg/kg/day) before or after the onset of neuropathy, whereas other diabetic rats received only isotonic saline as the same volume of GRL leaf extract. To evaluate the effects of GRL leaf extract on the diabetic neuropathy various parameters, including histopathology and immunohistochemistry of apoptotic and inflammatory factors were assessed along with nociceptive and biochemical assessments. RESULTS: Degeneration of the sciatic nerves which was detected in the STZ-diabetic rats attenuated after GRL leaf extract administration. Greater caspase-3, COX-2, and iNOS expression could be detected in the STZ-diabetic rats, which were significantly attenuated after GRL leaf extract administration. Also, attenuation of lipid peroxidation and nociceptive response along with improved antioxidant status in the sciatic nerve of diabetic rats were detected after GRL leaf extract administration. In other word, GRL leaf extract ameliorated the behavioral and structural indices of diabetic neuropathy even after the onset of neuropathy, in addition to blood sugar reduction. CONCLUSION: Our results suggest that GRL leaf extract exert preventive and curative effects against STZ-induced diabetic neuropathy in rats which might be due to its antioxidant, anti-inflammatory, and antiapoptotic properties. Protection against neuropathy.

Assessing advances in regional anesthesia by their portrayals in meta-analyses: an alternative view on recent progress.

BACKGROUND: The aim of this study was to delineate research reflecting advances in regional/local anesthesia where recent clinical progress was clearly defined by meta-analysis. METHODS: We conducted a search to identify all articles with meta-analyses of randomized clinical trials related to the field of regional/local anesthesia. From 279 titles, after multiple exclusions, 16 meta-analyses on important clinical practice developments with high potential for a positive conclusion on the effectiveness of the treatment were left for the assessment. The assessment was performed in two steps. The first step was related to verification of proof-of-concept: the effect is statistically reliable (p-value, effect size, heterogeneity across different RCTs) and the risk of bias not too high. The second step was devoted to attempts to form an opinion on the real clinical benefits of a new development. RESULTS: The assessment revealed that seven recent developments passed the proof-of-concept step. At the same time, positive conclusion on real clinical benefits was reached only by one of these seven developments: ultrasound guidance for peripheral nerve blocks (at least with some of the blocks). Meaningful clinical improvements with other developments remains uncertain. The assessment of the relationships between analyzed advancements over the past 30 years and earlier similar developments indicated that their evolution was usually incremental. The most original advancement was found to be the introduction of the transversus abdominis plane block. CONCLUSION: The assessment of recent advances in regional/local anesthesia, based on the evaluation of related meta-analyses, revealed only incremental progress with mostly marginal benefits. The progress was the most notable with ultrasound guidance for some of peripheral nerve blocks.

Vitamin D in the Spectrum of Prediabetes and Cardiovascular Autonomic Dysfunction.

Vitamin D is a fat-soluble secosteroid hormone with pleiotropic effects. 1,25-Dihydroxyvitamin D coordinates the biosynthesis of neurotransmitters in the central nervous system, which regulate cardiovascular autonomic function and may explain its putative role in the development of cardiovascular autonomic neuropathy (CAN). CAN is an independent risk factor for mortality in patients with diabetes and prediabetes and is associated with an increased risk of developing type 2 diabetes and cardiovascular disease. Accumulating data indicate the presence of peripheral nerve injury at these early stages of dysglycemia and its multifactorial pathogenesis. Prediabetes is associated with vitamin D insufficiency. Vitamin D is proposed to prevent the progression of glucose intolerance. The putative underlying mechanisms include maintenance of the intracellular calcium concentration, direct stimulation of insulin receptor expression, and enhancement of the insulin response to glucose transporters. Vitamin D exerts a protective effect on peripheral nerve fibers by decreasing the demyelination process and inducing axonal regeneration. The effects of vitamin D supplementation on glucose tolerance and related autonomic nerve dysfunction have been a recent focus of scientific interest. Although well-designed observational studies are available, the causative relation between vitamin D deficiency, glucose intolerance, and CAN is still debatable. One reason might be that interventional studies are unpersuasive with regard to the beneficial clinical effects of vitamin D supplementation. Because of its favorable side effect profile, vitamin D supplementation might represent an attractive therapeutic option for treating the pandemic prevalence of prediabetes and vitamin D deficiency. Vitamin D supplementation can improve glucose tolerance and cardiovascular autonomic function and can thus reduce cardiovascular mortality among subjects with different stages of glucose intolerance and autonomic dysfunction. However, more patient-centered trials on the use of vitamin D supplementation in different conditions are needed.

Selenium Ameliorate Peripheral Nerve Ischemic-Reperfusion Injury via Decreased TNF-α.

Selenium is considered as a trace element that plays antioxidant role in the body. So, the aim of this study was to evaluate the effect of selenium on ameliorating of sciatic nerve ischemia-reperfusion injury. Eighty (80) adult male Wistar rats weighing 250-300 g were used. They were divided into 10 groups (n = 8). Then, femoral vessels were obstructed by using 4/0 silk and splitknot techniques. After 3-h ischemia for all the groups, reperfusion was applied for different periods: 3, 7, 14, and 28 days. In half of each experimental group, 0.2 mg/kg selenium was injected intraperitoneally, coinciding with ischemia. After reperfusion, according to the grouping, rats were killed by using high dose of anesthetic drug and then sciatic nerve was removed and fixed. Then, tissue samples were processed and subsequently stained with hematoxylin-eosin, apoptosis, and immunohistochemistry stains. On the third day of reperfusion, the amount of TNF-α as an inflammatory marker of ischemia-reperfusion acute phase increased. On the seventh day of reperfusion, the amount of NF-кB as an apoptotic index and infiltration of mast cells increased in the tissue as a result of development of inflammation. But, on the 14th day of reperfusion, the amount of NF-кB as an apoptotic index decreased to the lowest amount. On the 28th day of reperfusion, the amount of TNF-α as an inflammatory marker decreased to its lowest level. Prescription of selenium concurrent with development of ischemia can reduce the damage caused by sciatic nerve ischemia-reperfusion.

Regional anesthesia practice in China: a survey.

STUDY OBJECTIVE: Neuraxial anesthesia has been widely used in China. Recently, Chinese anesthesiologists have applied nerve stimulator and ultrasound guidance for peripheral nerve blocks. Nationwide surveys about regional anesthesia practices in China are lacking. We surveyed Chinese anesthesiologists about regional anesthesia techniques, preference, drug selections, complications, and treatments. DESIGN: A survey was sent to all anesthesiologist members by WeChat. The respondents can choose mobile device or desktop to complete the survey. Each IP address is allowed to complete the survey once. MAIN RESULTS: A total of 6589 members read invitations. A total of 2654 responses were received with fully completed questionnaires, which represented an overall response rate of 40%. Forty-one percent of the respondents reported that more than 50% of surgeries in their hospitals were done under regional anesthesia. Most of the participants used test dose after epidural catheter insertion. The most common drug for test dose was 3-mL 1.5% lidocaine; 2.6% of the participants reported that they had treated a patient with epidural hematoma after neuraxial anesthesia. Most anesthesiologists (68.2%) performed peripheral nerve blocks as blind procedures based on the knowledge of anatomical landmarks. A majority of hospitals (80%) did not stock Intralipid; 61% of the respondents did not receive peripheral nerve block training. CONCLUSIONS: The current survey can serve as a benchmark for future comparisons and evaluation of regional anesthesia practices in China. This survey revealed potential regional anesthesia safety issues in China.

A New Proposal for Management of Severe Frostbite in the Austere Environment.

Despite advances in outdoor clothing and medical management of frostbite, individuals still experience catastrophic amputations. This is a particular risk for those in austere environments, due to resource limitations and delayed definitive treatment. The emerging best therapies for severe frostbite are thrombolytics and iloprost. However, they must be started within 24 hours after rewarming for recombinant tissue plasminogen activator (rt-PA) and within 48 hours for iloprost. Evacuation of individuals experiencing frostbite from remote environments within 24 to 48 hours is often impossible. To date, use of these agents has been confined to hospitals, thus depriving most individuals in the austere environment of the best treatment. We propose that thrombolytics and iloprost be considered for field treatment to maximize chances for recovery and reduce amputations. Given the small but potentially serious risk of complications, rt-PA should only be used for grade 4 frostbite where amputation is inevitable, and within 24 hours of rewarming. Prostacyclin has less risk and can be used for grades 2 to 4 frostbite within 48 hours of rewarming. Until more field experience is reported with these agents, their use should probably be restricted to experienced physicians. Other modalities, such as local nerve blocks and improving oxygenation at high altitude may also be considered. We submit that it remains possible to improve frostbite outcomes despite delayed evacuation using resource-limited treatment strategies. We present 2 cases of frostbite treated with rt-PA at K2 basecamp to illustrate feasibility and important considerations.

Does Magnesium Sulfate as an Adjuvant of Local Anesthetics Facilitate Better Effect of Perineural Nerve Blocks?: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVES: To investigate the efficacy and safety of magnesium sulfate as an adjuvant of local anesthetics in perineural nerve blocks. MATERIALS AND METHODS: Randomized controlled trials studying the effect and safety of magnesium sulfate in perineural nerve blocks were retrieved from online databases. The mean difference (MD), risk ratio, and their corresponding 95% confidence intervals (CIs) were calculated using RevMan 5.3 statistical software. RESULTS: Seven trials evaluating 493 patients were included. The pooled results from our meta-analysis showed that a combination of magnesium sulfate and local anesthetics in nerve blocks could result in longer postoperative duration time of analgesia (MD=124.66; 95% CI, 65.09-184.23; P<0.0001), longer duration time of sensory (MD=106.69; 95% CI, 60.93-152.45; P<0.00001) and motor block (MD=89.95; 95% CI, 50.89-129.00; P<0.0001). In addition, magnesium sulfate in nerve blocks was also associated with significantly quick onset of motor block (MD=-1.17; 95% CI, -1.73 to -0.60; P<0.0001). For onset time of sensory block, number of patients requiring supplementary analgesics, and incidence of postoperative nausea and vomiting, no statistically differences were observed between the 2 groups. DISCUSSION: The present study suggests that combined magnesium sulfate and local anesthetics in perineural nerve blocks provided better analgesic efficacy. For it prolongs the postoperative duration time of analgesia, sensory and motor block without increasing the short-term side effects. Magnesium sulfate may be a promising analgesic for perineural nerve blocks, but further studies are required to validate our results.