Dyspnea induced by hemidiaphragmatic paralysis after ultrasound-guided supraclavicular brachial plexus block in a morbidly obese patient.

RATIONALE: Hemidiaphragmatic paralysis (HDP) is a frequent complication of the brachial plexus block, caused by unintentional blockade of ipsilateral phrenic nerve. HDP did not rise enough alarm and attention to most anesthesiologists, because most patients with no coexisting comorbid diseases are asymptomatic and able to tolerate it. However, it may cause severe respiratory complication for patients with preexisting compromised cardiorespiratory function. PATIENT CONCERNS: A 67-year-old woman with morbidly obesity was planned to receive opening reduction and internal fixation of right humeral shaft fracture under regional anesthesia considering less respiratory and cardiovascular system interference compared with general anesthesia. DIAGNOSES: After ultrasound guided supraclavicular brachial plexus block, the patient developed severe hypoxia and hypercapnia.Unintentional block of phrenic nerve and diaphragm paralysis was diagnosed by diaphragm ultrasound, which was considered as the main reason of severe hypoxia. INTERVENTIONS: It led to a conversion from regional anesthesia to general anesthesia with endotracheal intubation for patient's safety and smooth operation. OUTCOMES: The unintentional phrenic nerve block leads to a prolonged ventilation time, length of stay in intensive care unit and length of stay in hospital. LESSONS: This case report highlights the risk of diaphragm paralysis in morbidly obese patients. Though new diaphragm sparing brachial plexus block (BPB) methods were developed intended to reduce the risk of HDP, no approaches could absolutely spare phrenic nerve involvement. Therefore, clinicians should always consider the risk of HDP associated with BPBs. For each individual, a detailed preoperative evaluation and sufficient preparation are paramount to avoid serious complications.

Real-time visualisation of peripheral nerve trauma during subepineural injection in pig brachial plexus using micro-ultrasound.

BACKGROUND: Nerve damage is consistently demonstrated after subepineural injection in animal studies, but not after purposeful injection in patients participating in clinical studies. There is a need to better visualise nerves in order to understand the structural changes that occur during subepineural injection. METHODS: We scanned the brachial plexuses of three anaesthetised pigs using micro-ultrasound imaging (55-22 MHz probe), inserted 21 gauge block needles into the radial, median, and axillary nerves, and injected two 0.5 ml boluses of saline into nerves at a rate of 12 ml min-1. Our objectives were to measure the area and diameter of nerves and fascicles, and to describe changes in nerve anatomy, comparing our findings with histology. RESULTS: Images were acquired at 42 sites across 18 nerves in three pigs and compared dimensions (geometric ratio; 95% confidence interval; P value). As expected, the nerve cross-sectional area was greater in the proximal brachial plexus compared with the mid-plexus (2.10; 1.07-4.11; P<0.001) and the distal plexus (2.64; 1.42-4.87; P<0.001). Nerve area expanded after 0.5 ml injection (2.13; 1.48-3.08; P<0.001). Using microultrasound, subepineural injection was characterised by nerve and fascicle rotation, uniform, or localised swelling and epineural rupture. Micro-ultrasound revealed a unique pattern suggestive of subperineural injection after a median nerve injection, and good face validity with histology. Histology showed epineural trauma and inflammation to the perineurium. CONCLUSION: We accurately identified fascicles and real-time structural changes to peripheral nerves using micro-ultrasound. This is the first study to visualise in vivo and in real-time the motion of nerves and fascicles in response to anaesthetic needle insertion and fluid injection.

NRG/ErbB signaling regulates neonatal muscle growth but not neuromuscular contractures in neonatal brachial plexus injury.

Neonatal brachial plexus injury (NBPI) causes disabling and incurable muscle contractures that are driven by impaired growth of denervated muscles. A rare form of NBPI, which maintains afferent muscle innervation despite motor denervation, does not cause contractures. As afferent innervation regulates various aspects of skeletal muscle homeostasis through NRG/ErbB signaling, our current study investigated the role of this pathway in modulating contracture development. Through pharmacologic modification with an ErbB antagonist and NRG1 isoforms, we discovered that NRG/ErbB signaling does not modulate the development of contractures in neonatal mice. Instead, ErbB inhibition impeded growth in nondenervated skeletal muscles, whereas increased ErbB activation exacerbated denervation-induced skeletal muscle atrophy. This potential regulatory effect of NRG/ErbB signaling on neonatal muscle growth warrants deeper investigation.

Assessment of the technique of the anesthetic block of the Brachial Plexus by Supraclavicular approach in Sapajus libidinosus (SPIX, 1823).

BACKGROUND: The aim of study was to evaluate the efficacy of the supraclavicular brachial plexus block technique in Sapajus libidinosus. METHODS: Were used eight animals, which were sedated, anesthetized, kept under hypnosis, and submitted to plexus block using a neurolocalizer. The physiological parameters, the nociception and response threshold (mA), were evaluated before and after the block. The response to electrical stimulation and cutaneous sensitivity were evaluated. The groups were compared by the Tukey or Friedman test at 5%. RESULTS: The technique promoted blockage of the plexus, and movement of the thoracic limb in response to electrical stimulation decreased after 10 minutes. The applied milliampere increased after 5 minutes. The cutaneous sensitivity reflex decreased. The average time of return of spontaneous limb movement exceeded 50 minutes. CONCLUSIONS: The use of 5mg/kg of lidocaine 2% promoted loss of cutaneous sensitivity and limb muscle relaxation during the evaluation period.

Trehalose protects motorneuron after brachial plexus root avulsion by activating autophagy and inhibiting apoptosis mediated by the AMPK signaling pathway.

Brachial plexus root avulsion (BPRA) is one of the most serious injuries of the upper extremity, which requires more effective treatment. Trehalose, a natural disaccharide, has reported to has a protective effect in neurodegenerative diseases. However, the effective effects and mechanism of trehalose on BPRA are still unclear. BPRA rat model were established, and then effects of trehalose on BPRA were investigated. TBHP-treated NSC34 cells with or without trehalose treatment were used for mechanism studies by Western blotting, Immunofluorescence and Flow cytometry analysis. Trehalose elevated the survival of motor neurons in rats after BPRA, suggesting a protective role of trehlose on BPRA. Trehalose treatment in rats after BPRA enhanced the autophage and thus inhibited apoptosis compared with rats in Vehicle group. Moreover, in TBHP-treated NSC34 cells, trehalose promoted the expression of autophage-related markers (LC3 and Beclin-1), concomitant with decreased levels of apoptosis. In vitro mechanism study indicated that the regulations of trehalose on autophage and apoptosis were via the AMPK-ULK1 pathway. Trehalose protects injured MNs by enhancing autophage and inhibiting apoptosis, which demonstrating the essential role of trehalose in the prevention and treatment of BPRA.

Localised delivery of quercetin by thermo-sensitive PLGA-PEG-PLGA hydrogels for the treatment of brachial plexus avulsion.

Accumulating evidence indicates that oxidative stress and inflammation are implicated in brachial plexus avulsion (BPA). Quercetin has anti-inflammatory, anti-oxidant, anti-apoptotic, and neuroprotective properties. This study investigated the therapeutic efficacy of a temperature-sensitive poly(D,L-lactide-co-glycolide)-poly(ethylene-glycol)-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) hydrogel sustained-release system of quercetin in BPA. In situ injections of the hydrogel loaded with different concentrations of quercetin were conducted in a rat model of BPA. Significantly reduced reactive oxygen species and interleukin-6 levels in the injured spinal cord 24 h post-surgery, increased number of anterior horn motor and functional neurons in the spinal cord 6 weeks post-surgery, thickened biceps muscle fibres and enlarged endplate area with clear structure, reduced demyelinated peripheral nerves, and significantly increased Terzis grooming test scores were found in the groups with 50 or 100 mg/mL quercetin-loaded hydrogels compared with the control and blank hydrogel groups. In conclusion, the temperature-sensitive quercetin loaded PLGA-PEG-PLGA hydrogel sustained-release system can alleviate oxidative damage and inflammation in the spinal cord, increase neuron survival rate, and promote nerve regeneration and motor function recovery in rats with early BPA. The findings suggest that this drug-loaded hydrogel has potential applications in the clinical treatment of BPA.

The effect of epinephrine on the perfusion index during ultrasound-guided supraclavicular brachial plexus block: a randomized controlled trial.

The perfusion index (PI) is an objective tool used to assess a successful nerve block. Epinephrine is a widely used adjuvant to local anesthetics, and it may affect PI values because of the vasoconstrictive property. The aim of this study was to investigate the influence of epinephrine on PI as an indicator of a successful block in ultrasound-guided supraclavicular brachial plexus block (SCBPB). In this randomized controlled trial, 82 adult patients underwent upper limb surgery under SCBPB were recruited between July 2018 and March 2019 in a single tertiary care center. Participants were randomly assigned to one of two groups: non-epinephrine group (n = 41) or epinephrine group (5 mcg ml-1, n = 41). The primary outcome was the comparison of the "PI ratio 10," which was defined as the ratio of the PI 10 to the baseline. Receiver operating characteristic (ROC) curves were constructed to determine the accuracy of the PI in predicting the block success at each time interval. The PI ratio 10 was 2.7 (1.9-4.0) in non-epinephrine group and 3.3 (2.2-4.4) in epinephrine group (median difference: 0.4; 95% confidence interval [CI] - 1.1 to 0.2; P = 0.207). The ROC curves compared without group identification were not significantly different over time. The cut-off value for the PI and PI ratio at 5 min (PI ratio 5) were 7.7 (area under the ROC [AUROC]: 0.89, 95% CI 0.83-0.94) and 1.6 (AUROC: 0.94, 95% CI 0.90-0.98), respectively. The perineural epinephrine did not affect the PI following a SCBPB. The PI ratio 5 > 1.6 might be considered as a relatively accurate predictor of a successful SCBPB.Trial registration: This study was registered at the Clinical Trial Registry of Korea (https://cris.nih.go.kr. CriS No. KCT0003006).

Comparison of ultrasound-guided supraclavicular and costoclavicular brachial plexus block using a modified double-injection technique: a randomized non-inferiority trial.

Ultrasound-guided costoclavicular block (CC-approach) is a recently described brachial plexus block (BPB) and an alternative approach to the supraclavicular approach (SC-approach). The relevant sonoanatomy is analogous in terms of the brachial plexus and its adjacent artery for both approaches. In the present study, we hypothesized that the two approaches will result in similar block dynamics when used the modified double-injection (MDI) technique. One hundred and twelve patients were randomly allocated to receive either a SC- or CC-approach with MDI technique. In the CC group, half the volume was injected adjacent to the medial cord of the brachial plexus, the procedure was guided by ultrasound and verified by nerve stimulator, subsequently the second half was injected close to the lateral cord. In the SC group, the MDI technique was carried out as described in our previous study. Sensory and motor blockade of all four terminal nerves were assessed with a 3-point scale. The primary outcome was the proportion of complete sensory blockade at 15 min with a predefined non-inferiority margin of -13%. The proportion of subjects at 15 min was comparable between the SC group and the CC group (91 vs 87%, absolute difference: -3%). No significant differences were found for complete motor blockade and onset times of the individual nerves within 30 min, and block-related serious adverse events (all P>0.05). We conclude that the MDI technique applied to a costoclavicular and supraclavicular block resulted in similar block dynamics. In addition, it may provide a promising alternative technique when considering the use of multipoint injection.

Neurogenic Thoracic Outlet Syndrome and other Forms of Cervical Brachial Syndrome Treated with Plasma Concentrate Enriched for Alpha 2 Macroglobulin.

BACKGROUND: Existing therapies for myofascial and neuralgic forms of cervicobrachial pain may have unsatisfactory outcomes. Alternative therapies may be considered, particularly for individuals who have failed to respond. Contemporary conceptualizations of chronic pain mechanisms include the contribution of inflammatory factors; therefore, locally targeted antiinflammatory administrations may play a role in treatment of cervicobrachial pain.Alpha 2 macroglobulin (A2M) is a plasma protein that acts as a molecular trap for inflammatory factors such as tumor necrosis factor. After plasma is enriched for A2M, it may be considered as a possible injectable agent to counteract inflammation that may occur with a cervicobrachial pain syndrome. OBJECTIVES: This retrospective review evaluates patient response to the use of plasma concentrate enriched for alpha 2 macroglobulin (A2M-PPP) in treatment of neurogenic thoracic outlet syndrome (TOS) and other forms of cervical brachial syndrome. STUDY DESIGN: Observational Study. SETTING: Outpatient interventional neurology practice. METHODS: There were 62 patients, including 46 women and 16 men ages 23-77 years. Twenty-three of these patients were diagnosed with complex regional pain syndrome (CRPS) or fibromyalgia, 18 with TOS, and 21 with musculotendinous pain (MTP). At baseline, 1 month, 3 months, and 6 months, patient status was evaluated with a Brief Pain Inventory (BPI) that included a composite pain score and a functional interference score. Patients were asked to estimate overall satisfaction with a Patient Global Impression of Change (PGIC) scale. Criterion for clinically significant improvement included >30% betterment in the BPI pain and functional interference subscales and a PGIC of > 5 at the 3-month mark. RESULTS: Three patients, one with CRPS and 2 with TOS, complained of several days of worsened pain or dysesthesias. No serious or permanent complications were encountered. For patients with TOS at the 3-month mark, 61% achieved clinical endpoints of success compared with 35% with CRPS/fibromyalgia and 24% for patients with MTP (P < 0.05, chi-square). By 6 months, 22% of individuals in the neuropathic TOS group had > 30% improvements in pain and functional interference scores compared with 13% of the individuals in the CRPS/fibromyalgia group and 18% in the MTP group. LIMITATIONS: This article does not differentiate the added benefit of A2M-PPP from hydrodissection alone. Additionally, this article does not evaluate the actual benefit of the A2M molecule apart from other factors present in the platelet-poor concentrate such as exosomes and cytokines. With the advent of pure engineered A2M, more focused studies will be possible. Also, an independent assay was not done, and therefore we cannot be precisely sure about the exact quantity of platelets, if any, which were contained in the platelet-poor concentration. CONCLUSIONS: Results suggest that A2M-PPP, when injected into muscle, tendon, and epineurium with live ultrasound guidance, appears to be relatively safe and free of postinjection inflammatory reactions that are often seen after platelet-poor plasma injection. A2M-PPP appears to be associated more frequently with good outcomes when injected into brachial plexus targets in patients with TOS compared with outcomes observed after injection of the plexus in patients with CRPS/fibromyalgia. KEY WORDS: Plasma concentrate enriched for alpha 2 macroglobulin, neurogenic thoracic outlet syndrome, cervical brachial syndrome.

Tissue Oxygen Saturation Change on Upper Extremities After Ultrasound-Guided Infraclavicular Brachial Plexus Blockade; Prospective Observational Study.

Background and Objective: The aim of this study was to investigate whether tissue oxygen saturation (StO2) is a reliable and objective method for assessing the adequacy of infraclavicular block and to describe the time course of StO2 changes. Materials and Methods: In this prospective observational study, StO2 was measured in 40 patients planned for elective hand surgery under infraclavicular block. Noninvasive StO2 monitoring was used prior to ultrasound-guided infraclavicular brachial plexus block and during the first 30 min of the blockade. Sensory and motor blocks were evaluated every 5 min followed by pinprick testing and Bromage scale. Results: Preanesthetic median StO2 values of the blocked side and nonblocked side were similar (p = 0.532), whereas the postanesthetic values of the blocked side were higher. At the fifth minute and the following minute, measurements compared to the nonblocked side (p < 0.001). The median StO2 values increased significantly, which increased by 4.5% at 5 min, by another 5.5% at 30 min, and by an average of 1% from 5 to 30 min compared to the baseline values in the blocked side. The responses of the patients to the questions probed in the pinprick test and Bromage scale were fully compatible with the data obtained by the near-infrared spectroscopy (NIRS) method. Conclusions: StO2 monitoring may provide a useful instrument for rapid evaluation of the success of regional anesthesia in the upper extremity.

Force perception at the shoulder after a unilateral suprascapular nerve block.

There are two key sources of information that can be used to match forces-the centrally generated sense of effort and afferent signals from mechanical receptors located in peripheral tissues. There is currently no consensus on which source of information is more important for matching forces. The corollary discharge hypothesis argues that subjects match forces using the centrally generated sense of effort. The purpose of this study was to investigate force matching at the shoulder before and after a suprascapular nerve block. The nerve block creates a sensory and muscle force mismatch between sides when matching loads. The torque matching accuracy did not change after the nerve block was administered. Directionally, the torque error was in the direction proposed by the corollary discharge hypothesis. However, the mismatch between deltoid EMG was substantially greater compared to the changes in the torque matching error after the block. The results support that sensory information is used during force matching tasks. However, since the nerve block also created a sensory disruption between sides, it is not clear how sensory information is reweighted following the nerve block and a role for sense of effort is still implicated.

The kinin B1 and B2 receptors and TNFR1/p55 axis on neuropathic pain in the mouse brachial plexus.

Tumour necrosis factor (TNF) and kinins have been associated with neuropathic pain-like behaviour in numerous animal models. However, the way that they interact to cause neuron sensitisation remains unclear. This study assessed the interaction of kinin receptors and TNF receptor TNFR1/p55 in mechanical hypersensitivity induced by an intraneural (i.n.) injection of rm-TNF into the lower trunk of brachial plexus in mice. The i.n. injection of rm-TNF reduced the mechanical withdrawal threshold of the right forepaw from the 3rd to the 10th day after the injection, indicating that TNF1/p55 displays a critical role in the onset of TNF-elicited neuropathic pain. The connection between TNF1/p55 and kinin B1 and B2 receptors (B1R and B2R) was confirmed using both knockout mice and mRNAs quantification in the injected nerve, DRG and spinal cord. The treatment with the B2R antagonist HOE 140 or with B1R antagonist des-Arg9-Leu8-BK reduced both BK- and DABK-induced hypersensitivity. The experiments using kinin receptor antagonists and CPM inhibitor (thiorphan) suggest that BK does not only activate B2R as an orthosteric agonist, but also seems to be converted into DABK that consequently activates B1R. These results indicate a connection between TNF and the kinin system, suggesting a relevant role for B1R and B2R in the process of sensitisation of the central nervous systems by the cross talk between the receptor and CPM after i.n. injection of rm-TNF.

Neuregulin-1 Accelerates Functional Motor Recovery by Improving Motoneuron Survival After Brachial Plexus Root Avulsion in Mice.

Brachial plexus root avulsion (BPRA) results in the complete loss of motor function in the upper limb, mainly due to the death of spinal motoneurons (MNs). The survival of spinal MNs is the key to the recovery of motor function. Neuregulin-1 (Nrg1) plays fundamental roles in nervous system development and nerve repair. However, its functional role in BPRA remains unclear. On the basis of our findings that Nrg1 is down-regulated in the ventral horn in a mouse model of BPRA, Nrg1 may be associated with BPRA. Here, we investigated whether recombinant Nrg1ß (rNrg1ß) can enhance the survival of spinal MNs and improve functional recovery in mice following BPRA. In vitro studies on primary cultured mouse MNs showed that rNrg1ß increased the survival rate in a dose-dependent manner, reaching a peak at 5 nM, which increased the survival rate and enhanced the pERK levels in MNs under H2O2-induced oxidative stress. In vivo studies revealed that rNrg1ß improved the functional recovery of elbow flexion, promoted the survival of MNs, enhanced the re-innervation of biceps brachii, and decreased the muscle atrophy. These results suggest that Nrg1 may provide a potential therapeutic strategy for root avulsion.

l-Theanine and NEP1-40 promote nerve regeneration and functional recovery after brachial plexus root avulsion.

Brachial plexus root avulsion causes severe sequelae Treatments and prognosis face many problems, including inflammatory reaction, oxidative damage, and myelin related inhibitory effect. l-Theanine has anti-inflammatory, anti-oxidative, and neuroprotective effects. NEP1-40 competitively inhibits Nogo-66 receptor (NgR1) promotes axonal regeneration. Forty-eight Sprague-Dawley rats were randomly assigned into four groups to establish an animal model of brachial plexus root avulsion. Inflammation and oxidative damage were evaluated by spectrophotometry and motor function of the upper limbs was assessed via Terzis grooming test after modeling. Immunofluorescence and hematoxylin and eosin staining were utilized to determine the content of reactive oxygen species, activation of microglial cells, neuroprotection, and nerve regeneration. Compared with the control group, the L-Theanine + NEP1-40 group had significantly decreased myeloperoxidase, malondialdehyde, interleukin-6, reactive oxygen species, and microglial cells, significantly increased score on the Terzis grooming test, increased motor neuron content, and thickened muscle fibers, increased area, and appearance of large and clear motor endplate structures. The results of this study suggest that l-Theanine combined with NEP1-40significantly promoted nerve regeneration after brachial plexus root avulsion, and may be a potential treatment for promoting nerve regeneration. Possible mechanisms underlying these results are alleviation of oxidative damage and inflammatory responses in the injured area and antagonism of myelin inhibition.