Efficacy of ultrasound-guided stellate ganglion block in relieving acute postoperative pain: a systematic review and meta-analysis.

OBJECTIVE: The efficacy of ultrasound-guided stellate ganglion block (SGB) in alleviating postoperative pain remains unclear. This meta-analysis was performed to determine the efficacy of ultrasound-guided SGB in relieving acute postoperative pain in patients undergoing surgery with general anesthesia. METHODS: This systematic review and meta-analysis focused on randomized controlled trials comparing SGB with control or placebo. The primary outcome was the pain score at 24 hours after surgery. A random-effects model was used to calculate the mean difference (MD) or risk ratio with a confidence interval (CI) of 95%. RESULTS: Eight studies involving 470 patients were included in the meta-analysis. The results revealed that ultrasound-guided SGB was significantly associated with a lower pain score at 24 hours after surgery (MD = -0.74; 95% CI = -1.39, -0.08; I2 = 86%; low evidence) and at 8 hours after surgery (MD = -0.65; 95% CI = -1.03, -0.28; I2 = 29%; moderate evidence). CONCLUSION: Ultrasound-guided SGB is effective in alleviating acute postoperative pain. However, considering the limited number of trials performed to date, more large-scale and high-quality randomized controlled trials are required to confirm these findings.

Safety and Efficacy of Ultrasound-Guided Sympathetic Blockade by Proximal Intercostal Block in Electrical Storm Patients.

BACKGROUND: Electrical storm (ES) patients who fail standard therapies have a high mortality rate. Previous studies report effective management of ES with bedside, ultrasound-guided percutaneous stellate ganglion block (SGB). We report our experience with sympathetic blockade administered via a novel alternative approach: proximal intercostal block (PICB). Compared with SGB, this technique targets an area typically free of other catheters and support devices, and may pose less strict requirements for anticoagulation interruption, along with lower risk of focal neurological side effects. OBJECTIVES: The authors sought to describe the safety and efficacy of PICB in patients with refractory ES. METHODS: We reviewed our institutional data on ES patients who underwent PICB between January 2018 and February 2023 to analyze procedural safety and short- and long-term outcomes. RESULTS: A total of 15 consecutive patients with ES underwent PICB during this period. Of those, 11 patients (73.3%) were maintained on PICB alone, and 4 patients (26.6%) were maintained on combined block with SGB and PICB. Overall, 72.7% patients who were maintained on PICB alone and 77.8% patients who were maintained on bilateral PICB had excellent arrhythmia suppression. After PICB, implantable cardioverter-defibrillator therapies were significantly reduced (P < 0.05), with 93.3% of patients receiving PICB having no implantable cardioverter-defibrillator shock until discharge or heart transplant. Anticoagulation was continued in all patients and there were no procedure-related complications. Apart from mild transient neurological symptoms seen in 3 patients, no significant neurological or hemodynamic sequelae were observed. CONCLUSIONS: In patients with refractory ES, continuous PICB provided safe and effective sympathetic block (77.8% ventricular arrhythmia suppression), achievable without interruption of anticoagulation, and without significant side effects.

Interventions for the management of abdominal pain in ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammation of the colon characterised by periods of relapse and remission. It starts in the rectum and can extend throughout the colon. UC and Crohn's disease (CD) are the most common inflammatory bowel diseases (IBDs). However, UC tends to be more common than CD. It has no known cure but can be managed with medication and surgery. However, studies have shown that abdominal pain persists in up to one-third of people with UC in remission. Abdominal pain could be a symptom of relapse of the disease due to adverse effects of medication, surgical complications and strictures or adhesions secondary to UC. OBJECTIVES: To assess the efficacy and safety of interventions for managing abdominal pain in people with ulcerative colitis. SEARCH METHODS: We searched CENTRAL, MEDLINE and five other databases and clinical trials registries on 28 April 2021. We contacted authors of relevant studies and ongoing or unpublished trials that may be relevant to the review. We also searched references of trials and systematic reviews for any additional trials. SELECTION CRITERIA: All published, unpublished and ongoing randomised trials that compared interventions for the management of abdominal pain with other active interventions or standard therapy, placebo or no therapy were included. People with both active and inactive disease were included. We excluded studies that did not report on any abdominal pain outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently conducted data extraction and 'Risk of bias' assessments. We analysed data using Review Manager 5. We expressed dichotomous and continuous outcomes as risk ratios (RRs) and mean differences (MDs), respectively, with 95% confidence intervals. We assessed the certainty of the evidence using the GRADE methodology. MAIN RESULTS: We included five studies (360 randomised participants). Studies considered mainly participants in an inactive state of the disease.   No conclusions could be drawn about the efficacy of any of the interventions on pain frequency, pain intensity, and treatment success. The certainty of the evidence was very low for all comparisons because of imprecision due to sparse data, and risk of bias. One study compared a low FODMAPs diet (n=13) to a sham diet (n=13). The evidence is very uncertain about the effect of this treatment on pain frequency (MD -4.00, 95% CI -20.61 to 12.61) and intensity (MD -9.00, 95% CI -20.07 to 2.07). Treatment success was not reported. One study compared relaxation training (n=20) to wait-list (n=20). The evidence is very uncertain about the effect of this treatment on pain frequency at end of intervention (MD 2.60, 95% CI 1.14 to 4.06) and 6-month follow-up (MD 3.30, 95% CI 1.64 to 4.96). Similarly, the evidence is very uncertain about the effect of this treatment on pain intensity at end of intervention (MD -1.70, 95% CI -2.92 to -0.48) and 6-month follow-up (MD -2.30, 95% CI -3.70 to -0.90). Treatment success was not reported. One study compared yoga (n=30) to no intervention (n=30). The study defined treatment success as the presence or absence of pain; however, the data they provided was unclear. Pain frequency and intensity were not reported. One study compared a kefir diet (Lactobacillus bacteria, n=15) to no intervention (n=15). The evidence is very uncertain about the effect of this treatment on pain intensity (MD -0.17, 95% CI -0.91 to 0.57). Pain frequency and treatment success were not reported. One study compared a stellate ganglion block treatment (n=90) to sulfasalazine treatment (n=30). The study defined treatment success as "stomachache"; however, the data they provided was unclear. Pain frequency and intensity were not reported. Two studies reported withdrawals due to adverse events. One study reported withdrawals due to adverse events as zero. Two studies did not report this outcome.  We cannot draw any conclusions about the effects of any of the interventions on withdrawals due to adverse events because of the very limited evidence. The reporting of secondary outcomes was inconsistent. Adverse events tended to be very low or zero. However, we can make no clear judgements about adverse events for any of the interventions, due to the low number of events. Anxiety was measured and reported at end of intervention in only one study (yoga versus no intervention), and depression was not measured in any of the studies. We can therefore draw no meaningful conclusions about these outcomes. AUTHORS' CONCLUSIONS: We found very low-certainty evidence on the efficacy and safety of interventions for the management of abdominal pain in ulcerative colitis. Pervasive issues with very serious imprecision from small samples size and high risk of bias have led to very low-certainty outcomes, precluding conclusions. While few adverse events and no serious adverse events were reported, the certainty of these findings was again very low for all comparisons, so no conclusions can be drawn. There is a need for further research. We have identified eight ongoing studies in this review, so an update will be warranted. It is key that future research addresses the issues leading to reduced certainty of outcomes, specifically sample size and reporting that leads to high risk of bias. It is also important that if researchers are considering pain as a critical outcome, they should report clearly if participants were pain-free at baseline; in that case, data would be best presented as separate subgroups throughout their research.

Macrophage depletion in stellate ganglia alleviates cardiac sympathetic overactivation and ventricular arrhythmogenesis by attenuating neuroinflammation in heart failure.

Cardiac sympathetic overactivation is involved in arrhythmogenesis in patients with chronic heart failure (CHF). Inflammatory infiltration in the stellate ganglion (SG) is a critical factor for cardiac sympathoexcitation in patients with ventricular arrhythmias. This study aims to investigate if macrophage depletion in SGs decreases cardiac sympathetic overactivation and ventricular arrhythmogenesis in CHF. Surgical ligation of the coronary artery was used for induction of CHF. Clodronate liposomes were microinjected into bilateral SGs of CHF rats for macrophage depletion. Using cytokine array, immunofluorescence staining, and Western blot analysis, we found that macrophage expansion and expression of TNFα and IL-1ß in SGs were markedly increased in CHF rats. Flow cytometry data confirmed that the percentage of macrophages in SGs was higher in CHF rats than that in sham rats. Clodronate liposomes significantly reduced CHF-elevated proinflammatory cytokine levels and macrophage expansion in SGs. Clodronate liposomes also reduced CHF-increased N-type Ca2+ currents and excitability of cardiac sympathetic postganglionic neurons and inhibited CHF-enhanced cardiac sympathetic nerve activity. ECG data from 24-h, continuous telemetry recording in conscious rats demonstrated that clodronate liposomes not only restored CHF-induced heterogeneity of ventricular electrical activities, but also decreased the incidence and duration of ventricular tachycardia/fibrillation in CHF. Macrophage depletion with clodronate liposomes attenuated CHF-induced cardiac sympathetic overactivation and ventricular arrhythmias through reduction of macrophage expansion and neuroinflammation in SGs.

Developmental exposure to DDT or DDE alters sympathetic innervation of brown adipose in adult female mice.

BACKGROUND: Exposure to the bioaccumulative pesticide dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorodiphenyldichloroethylene (DDE) has been associated with increased risk of insulin resistance and obesity in humans and experimental animals. These effects appear to be mediated by reduced brown adipose tissue (BAT) thermogenesis, which is regulated by the sympathetic nervous system. Although the neurotoxicity of DDT is well-established, whether DDT alters sympathetic innervation of BAT is unknown. We hypothesized that perinatal exposure to DDT or DDE promotes thermogenic dysfunction by interfering with sympathetic regulation of BAT thermogenesis. METHODS: Pregnant C57BL/6 J mice were administered environmentally relevant concentrations of DDTs (p,p'-DDT and o,p'-DDT) or DDE (p,p'-DDE), 1.7 mg/kg and 1.31 mg/kg, respectively, from gestational day 11.5 to postnatal day 5 by oral gavage, and longitudinal body temperature was recorded in male and female offspring. At 4 months of age, metabolic parameters were measured in female offspring via indirect calorimetry with or without the ß3 adrenergic receptor agonist, CL 316,243. Immunohistochemical and neurochemical analyses of sympathetic neurons innervating BAT were evaluated. RESULTS: We observed persistent thermogenic impairment in adult female, but not male, mice perinatally exposed to DDTs or p,p'-DDE. Perinatal DDTs exposure significantly impaired metabolism in adult female mice, an effect rescued by treatment with CL 316,243 immediately prior to calorimetry experiments. Neither DDTs nor p,p'-DDE significantly altered BAT morphology or the concentrations of norepinephrine and its metabolite DHPG in the BAT of DDTs-exposed mice. However, quantitative immunohistochemistry revealed a 20% decrease in sympathetic axons innervating BAT in adult female mice perinatally exposed to DDTs, but not p,p'-DDE, and 48 and 43% fewer synapses in stellate ganglia of mice exposed to either DDTs or p,p'-DDE, respectively, compared to control. CONCLUSIONS: These data demonstrate that perinatal exposure to DDTs or p,p'-DDE impairs thermogenesis by interfering with patterns of connectivity in sympathetic circuits that regulate BAT.

Neurotoxicity studies with a tropomyosin-related kinase A inhibitor, ASP7962, on the sympathetic and sensory nervous systems in rats.

ASP7962 is a small molecule inhibitor for the nerve growth factor (NGF) receptor, tropomyosin-related kinase A (TrkA). NGF contributes to the survival of sensory and sympathetic neurons through TrkA receptor activation. Gross, microscopic, and quantitative effects to the nervous system were evaluated following oral ASP7962 administration to Sprague Dawley rats for 4 weeks and 13 weeks and after a recovery period. Histopathological findings included reversible neuronal atrophy but no neuronal death in the sympathetic ganglia (cervicothoracic ganglion, cranial mesenteric ganglion or superior [cranial] cervical ganglion). Stereological analysis showed reversible decreased ganglion volume and/or decreased neuron size in the superior (cranial) cervical ganglion in both the 4-week and the 13-week repeated dose studies. There were no test article related changes in the brain, dorsal root ganglia with spinal nerve roots or trigeminal ganglia and no functional deficits. ASP7962 did not cause any detectable dysfunction of the sympathetic and sensory nervous system in either study.

Effects of stellate ganglion block on early brain injury in patients with subarachnoid hemorrhage: a randomised control trial.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a common neurosurgical emergency, and early brain injury (EBI) plays an important role in acute brain injury of SAH. Our objective is to investigate the effect of stellate ganglion block (SGB) on the clinical prognosis of patients with SAH (registration number ChiCTR2000030910). METHODS: A randomized controlled trial was conducted with 102 participants. Patients with SAH were assigned to the SGB or nSGB group. Patients in the SGB group received SGB four times (once every other day starting on the day of the surgery). In contrast, patients in the nSGB group only received standard care. Data were collected on the day before surgery (T0) and on the 1st (T1), 3rd (T2) and 7th day (T3) after surgery. The primary outcomes included EBI markers (including IL-1ß, IL-6, TNF-α, ET-1, NPY, NSE and S100ß), the mean cerebral blood flow velocity of the middle cerebral artery (Vm-MCA) and the basilar artery (Vm-BA). All cases were followed up for 6 months after surgery. RESULTS: The levels of the EBI markers in both groups were higher at T1-T3 than at T0 (P<0.05), and the Vm-MCA and Vm-BA were also increased at the same times. However, the levels of the EBI markers were lower in the SGB group than in the nSGB group (P<0.05), and the increases of Vm-MCA and Vm-BA were also lower (P<0.05). The prognosis score and neurological deficit were better in the SGB group than in the nSGB group (P<0.05). CONCLUSIONS: SGB can improve the prognosis of SAH patients by inhibiting the inflammatory response during EBI and by reducing endothelial dysfunction and relieving CVS. TRIAL REGISTRATION: Clinical trial number: ChiCTR2000030910 ; Registry URL: Chinese Clinical Trial Registry; Principal investigator's name: Ying Nie; Date of Trial registration: March, 2020 (retrospectively registered).

Stellate Ganglion Blockade repairs Intestinal Mucosal Barrier through suppression of Endoplasmic Reticulum Stress following Hemorrhagic Shock.

Background: Hemorrhagic shock-induced ischemia and hypoxia elicit endoplasmic reticulum stress (ERS) that leads to cell apoptosis, tissue structural damage and organ dysfunction and failure. Stellate ganglion blockade (SGB) has been demonstrated to improve intestinal barrier dysfunction induced by hemorrhagic shock. The present study sought to investigate whether the beneficial effect of SGB on the intestinal mucosal barrier function is via suppression of ERS. Materials and methods: A conscious rat model of hemorrhagic shock (40 ±2 mmHg for 1 hour, followed by resuscitation) was established. The parameters reflecting intestinal morphology and intestinal mucosal barrier function including wet-dry ratio (W/D), intestinal permeability, D-lactic acid (D-LA) and intestinal fatty acid binding protein (I-FABP) in plasma, and expressions of ATF6α, PERK, and IRE1α in intestinal tissues were then observed. Furthermore, the effects of either SGB or ERS inhibitor, 4-phenylbutyric acid (4-PBA), on these parameters in rats with hemorrhagic shock were assessed. The effect of ERS agonist tunicamycin (TM) on the rats subjected with both SGB and hemorrhagic shock was also determined. Results: Either SGB or administration of ERS inhibitor, 4-PBA, alleviated hemorrhagic shock-induced adverse effects such as intestinal mucosal barrier dysfunction and excessive autophagy, which were characterized by damaged intestinal tissue, enhanced intestinal permeability and D-LA and I-FABP levels in plasma, and increased expressions of ATF6α, PERK, IRE1α in intestinal tissue. In contrast, administration of ERS agonist, TM, suppressed the beneficial effects of SGB on intestinal tissue and function during hemorrhagic shock. Conclusion: The SGB repairs intestinal mucosal barrier through suppression of ERS following hemorrhagic shock.

Effects of Stellate Ganglion Block on Healing of Fractures Induced in Rats.

OBJECTIVE: Sympathetic blocks are used as an adjunct for pain management in the treatment of orthopedic and traumatic conditions. Stellate ganglion (ganglion stellatum) provides sympathetic innervation of the head, neck and cervicothoracic regions, and upper extremities. No study was found in the literature investigating the effects of stellate ganglion block performed in the upper extremity, on blood supply to bone, density, vascularization, and bone metabolism. Therefore, the objective of this study was to investigate the effects of stellate ganglion block on healing of closed forearm fractures that were induced in rats. Material and Methods. A total of 42 Wistar albino rats weighing between 398 and 510 g were used in this study. The rats were randomly divided into 2 groups with one group treated with stellate ganglion and the other included as the control group. In each 2 groups, a closed forearm fracture was created, confirmed with X-ray, and then stabilized by splint application. The forearm bones were examined with X-ray views on the same day and were then decalcified. RESULTS: When histological findings of the fracture region were examined, predominantly cartilage and less woven bone were found in 7 rats, equally distributed cartilage and immature bone in 14 rats, and predominantly imitation bone and less cartilage formation in 21 rats. In the control group, the agreement between the 1st and 2nd orthopedists for the radiological evaluation of bone formation was moderate. CONCLUSION: The group administered stellate ganglion block showed a more significant fracture healing.

Effects of stellate ganglion block on postoperative trigeminal neuropathy after dental surgery: a propensity score matching analysis.

This study aimed to evaluate the effects of stellate ganglion block (SGB) on postoperative trigeminal neuropathy (TNP) after dental surgery. This was a retrospective study based on the medical records of all patients with postoperative TNP at Kyushu Dental University Hospital from 2014 to 2019. Patients were divided into the SGB group (received SGB) and non-SGB group (did not receive SGB). We evaluated the severity of TNP at 3 months after surgery and the incidence rate of abnormal sensations. Abnormal sensations were counted using patients' reports of uncomfortable symptoms during the treatment, including dysaesthesia, allodynia, and hyperalgesia. A propensity score (PS) matching analysis was performed to evaluate these data. After PS matching, amongst others, the force equivalent values of the Semmes-Weinstein test at 3-months post-treatment were significantly lower in the SGB group than in the non-SGB group (2.00 ± 0.44 vs 2.30 ± 0.48; p < 0.05). In addition, after PS matching, the incidence rate of abnormal sensations during the treatment was significantly lower in the SGB group than in the non-SGB group (10 cases [4.7%] vs 22 cases [10.3%]; p < 0.05). Collectively, the findings support that SGB may improve the recovery from postoperative TNP and reduce the incidence rate of abnormal sensations after dental surgery.

Effectiveness, Safety, and Predictive Potential in Ultrasound-Guided Stellate Ganglion Blockades for the Treatment of Sympathetically Maintained Pain.

BACKGROUND: Evaluating the effectiveness of stellate ganglion blockades (SGBs) proves challenging, since the criteria defining a successful blockade are controversial. This may be one reason for the scarcity of studies on this topic, thus forcing clinical guidelines to remain conservative in recommending SGBs. Moreover, factors to predict which patients will benefit from blockade series are not yet available. OBJECTIVES: The objectives of this study were to evaluate through a clinical approach SGBs' effectiveness performed under ultrasound guidance (us-SGB) and to identify factors to predict effectiveness. METHODS: We retrospectively analyzed 809 us-SGBs in 105 patients with complex regional pain syndrome (CRPS) and neuropathic pain syndromes (all potentially including sympathetically maintained pain) regarding pain reduction. Volume and type of local anesthetics, magnitude of pain, temperature of the dorsal hands, heart rate, blood pressure, and occurrence of Horner's syndrome or complications were assessed. RESULTS: Pain reduction after a blockade series was highly significant and showed no significant correlation with change of temperature, vital signs, or Horner's syndrome. For patients with neuropathic pain, the predictive potential for pain reduction following a blockade series lies within the range of pain reduction after the first blockade. In a literature comparison, incidences of complications (hoarseness 3.9%, dysphagia 3.4%, hematoma 0.6%) were lower than in non-ultrasound-guided techniques. CONCLUSIONS: Data indicate that us-SGBs are safe and effective in reducing sympathetically maintained pain in patients with CRPS and neuropathic pain syndromes. Pain reduction after the first blockade may predict total pain reduction after a blockade series. Other clinical measures seem unsuitable to predict effectiveness.

Preoperative Stellate Ganglion Block for Perioperative Pain in Lateralized Head and Neck Cancer: Preliminary Results.

Patients with head and neck cancer represent a vulnerable population at particular risk of opioid dependence due to frequent histories of substance abuse, requirement of extensive surgery, and the synergistic toxicity of multimodal therapy. Regional anesthetic techniques have been used by other surgical disciplines to facilitate early recovery after surgery and decrease postoperative patient narcotic requirements. This pilot study investigates the efficacy of a preoperative regional analgesia using stellate ganglion block in lateralized head and neck cancer surgery. From our early results, stellate ganglion blockade may hold promise as an effective preoperative intervention for controlling early postoperative pain, lessening narcotic requirements, and improving quality of life.

Effect of Stellate Ganglion Block Treatment on Posttraumatic Stress Disorder Symptoms: A Randomized Clinical Trial.

Importance: This is the first multisite, randomized clinical trial of stellate ganglion block (SGB) outcomes on posttraumatic stress disorder (PTSD) symptoms. Objective: To determine whether paired SGB treatments at 0 and 2 weeks would result in improvement in mean Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total symptom severity scores from baseline to 8 weeks. Design, Setting, and Participants: This multisite, blinded, sham-procedure, randomized clinical trial used a 2:1 SGB:sham ratio and was conducted from May 2016 through March 2018 in 3 US Army Interdisciplinary Pain Management Centers. Only physicians performing the procedures and the procedure nurses were aware of the intervention (but not the participants or assessors); their interactions with the participants were scripted and limited to the 2 interventions. Active-duty service members on stable psychotropic medication dosages who had a PTSD Checklist-Civilian Version (PCL-C) score of 32 or more at screening were included. Key exclusion criteria included a prior SGB treatment, selected psychiatric disorders or substance use disorders, moderate or severe traumatic brain injury, or suicidal ideation in the prior 2 months. Interventions: Paired right-sided SGB or sham procedures at weeks 0 and 2. Main Outcomes and Measures: Improvement of 10 or more points on mean CAPS-5 total symptom severity scores from baseline to 8 weeks, adjusted for site and baseline total symptom severity scores (planned a priori). Results: Of 190 screened individuals, 113 (59.5%; 100 male and 13 female participants; mean [SD] age, 37.3 [6.7] years) were eligible and randomized (74 to SGB and 39 to sham treatment), and 108 (95.6% of 113) completed the study. Baseline characteristics were similar in the SGB and sham treatment groups, with mean (SD) CAPS-5 scores of 37.6 (11.2) and 39.8 (14.4), respectively (on a scale of 0-80); 91 (80.0%) met CAPS-5 PTSD criteria. In an intent-to-treat analysis, adjusted mean total symptom severity score change was -12.6 points (95% CI, -15.5 to -9.7 points) for the group receiving SGB treatments, compared with -6.1 points (95% CI, -9.8 to -2.3 points) for those receiving sham treatment (P = .01). Conclusions and Relevance: In this trial of active-duty service members with PTSD symptoms (at a clinical threshold and subthreshold), 2 SGB treatments 2 weeks apart were effective in reducing CAPS-5 total symptom severity scores over 8 weeks. The mild-moderate baseline level of PTSD symptom severity and short follow-up time limit the generalizability of these findings, but the study suggests that SGB merits further trials as a PTSD treatment adjunct. Trial Registration: ClinicalTrials.gov identifier: NCT03077919.

Stellate ganglion block and cardiac sympathetic denervation in patients with inappropriate sinus tachycardia.

BACKGROUND: Inappropriate sinus tachycardia (IST) remains a clinical challenge because patients often are highly symptomatic and not responsive to medical therapy. OBJECTIVE: To study the safety and efficacy of stellate ganglion (SG) block and cardiac sympathetic denervation (CSD) in patients with IST. METHODS: Twelve consecutive patients who had drug-refractory IST (10 women) were studied. According to a prospectively initiated protocol, five patients underwent an electrophysiologic study before and after SG block (electrophysiology study group). The subsequent seven patients had ambulatory Holter monitoring before and after SG block (ambulatory group). All patients underwent SG block on the right side first, and then on the left side. Selected patients who had heart rate reduction ≥15 beats per minute (bpm) were recommended to consider CSD. RESULTS: The mean (SD) baseline heart rate (HR) was 106 (21) bpm. The HR significantly decreased to 93 (20) bpm (P = .02) at 10 minutes after right SG block and remained significantly slower at 97(19) bpm at 60 minutes. Left SG block reduced HR from 99 (21) to 87(16) bpm (P = .02) at 60 minutes. SG block had no significant effect on blood pressure or HR response to isoproterenol or exercise (all P > .05). Five patients underwent right (n = 4) or bilateral (n = 1) CSD. The clinical outcomes were heterogeneous: one patient had complete and two had partial symptomatic relief, and two did not have improvement. CONCLUSION: SG blockade modestly reduces resting HR but has no significant effect on HR during exercise. Permanent CSD may have a modest role in alleviating symptoms in selected patients with IST.

A Prospective, Randomized Cross-Over Trial of T2 Paravertebral Block as a Sympathetic Block in Complex Regional Pain Syndrome.

BACKGROUND: Sympathetic block is commonly performed in clinical practice for management of intractable pain conditions. However, stellate ganglion block (SGB) alone often does not achieve sufficient sympatholysis of the upper extremity. The paravertebral space continues up to the cervical sympathetic chain and includes the stellate ganglion. We compared the sympatholytic and analgesic effect of paravertebral block performed at the T2 level (T2 PVB) with that of SGB in patients with complex regional pain syndrome (CRPS) of the upper extremity. OBJECTIVES: The aim of this study was to compare the sympatholytic property of T2 PVB with that of the conventional SGB in patients with CRPS of the upper extremity. STUDY DESIGN: Prospective, randomized cross-over trial. SETTING: University hospital pain center in Korea. METHODS: Fifteen patients with upper extremity CRPS were randomly assigned to 1 of 2 intervention methods (SGB or T2 PVB). After effects of the first block receded, the patients were crossed over to the second procedure. A difference in temperature increase between the treated side and the opposite side (DeltaT) DeltaT greater than or equal to1.5°C was considered as a successful primary outcome. Rate of successful primary outcome, degree of pain reduction, duration of effect, and patient satisfaction scores were compared between the 2 intervention methods. RESULTS: Rate of successful primary outcome (DeltaT greater than or equal to 1.5°C) was significantly higher in the T2 PVB cases than in the SGB cases (80.0% vs. 20.0%; P = 0.003). Numeric Rating Scale scores after the procedure were significantly lower in the T2 PVB group. Patient satisfaction scores were significantly higher, and the duration of the block was significantly longer in the T2 PVB cases than in the SGB cases. LIMITATIONS: The relatively small sample size from a single center, and the lack of standardization of the injected volume of T2 PVB and SGB were limitations. CONCLUSIONS: T2 PVB showed superior sympatholytic effect than SGB; other clinical outcomes were also better with T2 PVB than with SGB. T2 PVB can be a useful option for producing sympatholytic and analgesic effect in patients with CRPS of the upper extremity. KEY WORDS: Sympathetic block, Complex Regional Pain Syndrome, paravertebral block, stellate ganglion block.

Blockade of Stellate Ganglion Remediates Hemorrhagic Shock-Induced Intestinal Barrier Dysfunction.

BACKGROUND: Acute hemorrhage-induced excessive excitation of sympathetic-adrenal-medullary system (SAS) leads to gut hypoperfusion and barrier dysfunction, which is a critical event during hemorrhagic shock-induced multiple organ injury. Stellate ganglion blockade (SGB) has been widely used for suppression of sympathetic-adrenal-medullary system in the clinical practice. However, whether SGB improves intestinal barrier function after hemorrhagic shock remains unclear. Here, we hypothesized that the implementation of SGB restores intestinal barrier function and reduces gut injury. MATERIALS AND METHODS: Male rats received the SGB pretreatment and underwent hemorrhagic shock followed by resuscitation. The 96-h survival rate, intestinal permeability and morphology, D-lactic acid concentration and diamine oxidase activity in plasma, and expressions of F-actin, Claudin-1, and E-cadherin in intestinal tissues were observed. RESULTS: Pretreatment with SGB significantly enhances the 96-h survival rate in rats subjected to hemorrhagic shock (from 8.3% to 66.7%). Hemorrhagic shock reduced the coverage scale of intestinal mucus and intestinal villus width and height, enhanced the intestinal permeability to fluorescein isothiocyanate-dextran 4 and D-lactic acid concentration in plasma, and decreased the expressions of F-actin, Claudin-1, and E-Cadherin in intestinal tissue. These hemorrhagic shock-induced adverse effects were abolished by SGB treatment. CONCLUSIONS: SGB treatment has a beneficial effect during hemorrhagic shock, which is associated with the improvement of intestine barrier function. SGB may be considered as a new therapeutic strategy for treatment of hemorrhagic shock.

Effects of anesthetic and sedative agents on sympathetic nerve activity.

BACKGROUND: The effects of sedative and anesthetic agents on sympathetic nerve activity (SNA) are poorly understood. OBJECTIVE: The purpose of this study was to determine the effects of commonly used sedative and anesthetic agents on SNA in ambulatory dogs and humans. METHODS: We implanted radiotransmitters in 6 dogs to record stellate ganglion nerve activity (SGNA), subcutaneous nerve activity (ScNA), and blood pressure (BP). After recovery, we injected dexmedetomidine (3 µg/kg), morphine (0.1 mg/kg), hydromorphone (0.05 mg/kg), and midazolam (0.1 mg/kg) on different days. We also studied 12 human patients (10 male; age 68.0 ± 9.1 years old) undergoing cardioversion for atrial fibrillation with propofol (0.77 ± 0.18 mg/kg) or methohexital (0.65 mg/kg) anesthesia. Skin sympathetic nerve activity (SKNA) and electrocardiogram were recorded during the study. RESULTS: SGNA and ScNA were significantly suppressed immediately after administration of dexmedetomidine (P = .000 and P = .000, respectively), morphine (P = .011 and P = .014, respectively), and hydromorphone (P = .000 and P = .012, respectively), along with decreased BP and heart rate (HR) (P <.001 for each). Midazolam had no significant effect on SGNA and ScNA (P = .248 and P = .149, respectively) but increased HR (P = .015) and decreased BP (P = .004) in ambulatory dogs. In patients undergoing cardioversion, bolus propofol administration significantly suppressed SKNA (from 1.11 ± 0.25 µV to 0.77 ± 0.15 µV; P = .001), and the effects lasted for at least 10 minutes after the final cardioversion shock. Methohexital decreased chest SKNA from 1.59 ± 0.45 µV to 1.22 ± 0.58 µV (P = .000) and arm SKNA from 0.76 ± 0.43 µV to 0.55 ± 0.07 µV (P = .001). The effects lasted for at least 10 minutes after the cardioversion shock. CONCLUSION: Propofol, methohexital, dexmedetomidine, morphine, and hydromorphone suppressed, but midazolam had no significant effects on, SNA.

Effects of tanezumab on satellite glial cells in the cervicothoracic ganglion of cynomolgus monkeys: A 26-week toxicity study followed by an 8-week recovery period.

Tanezumab, a humanized monoclonal anti-NGF antibody, has demonstrated efficacy and safety profiles in Phase III clinical trials of chronic pain. In a 24-week study in non-human primates, morphological observations of sympathetic ganglia showed decreased ganglia volume, decreased neuronal size, and increased glial cell density compared with controls after 3 tanezumab treatments. Using stereological techniques to quantify glial cells, the present 26-week study found no significant difference after weekly treatments in total cervicothoracic ganglia satellite glial cell number between placebo- or tanezumab-treated cynomolgus monkeys. These findings suggest that tanezumab treatment does not result in a true gliosis in sympathetic ganglia.

Proarrhythmic proclivity of left-stellate ganglion stimulation in a canine model of drug-induced long-QT syndrome type 1.

BACKGROUND: Left-stellate ganglion stimulation (LSGS) can modify regional dispersion of ventricular refractoriness, promote triggered activity, and reduce the threshold for ventricular fibrillation (VF). Sympathetic hyperactivity precipitates torsades de pointes (TdP) and VF in susceptible patients with long-QT syndrome type 1 (LQT1). We investigated the electromechanical effects of LSGS in a canine model of drug-induced LQT1, gaining novel arrhythmogenic insights. METHODS: In nine mongrel dogs, the left and right stellate ganglia were exposed for electrical stimulation. ECG, left- and right-ventricular endocardial monophasic action potentials (MAPs) and pressures (LVP, RVP) were recorded. The electromechanical window (EMW; Q to LVP at 90% relaxation minus QT interval) was calculated. LQT1 was mimicked by infusion of the KCNQ1/IKs blocker HMR1556. RESULTS: At baseline, LSGS and right-stellate ganglion stimulation (RSGS) caused similar heart-rate acceleration and QT shortening. Positive inotropic and lusitropic effects were more pronounced under LSGS than RSGS. IKs blockade prolonged QTc, triggered MAP-early afterdepolarizations (EADs) and rendered the EMW negative, but no ventricular tachyarrhythmias occurred. Superimposed LSGS exaggerated EMW negativity and evoked TdP in 5/9 dogs within 30 s. Preceding extrasystoles originated mostly from the outflow-tracts region. TdP deteriorated into therapy-refractory VF in 4/5 animals. RSGS did not provoke TdP/VF. CONCLUSIONS: In this model of drug-induced LQT1, LSGS readily induced TdP and VF during repolarization prolongation and MAP-EAD generation, but only if EMW turned from positive to very negative. We postulate that altered mechano-electric coupling can exaggerate regional dispersion of refractoriness and facilitates ventricular ectopy.

The effects of interleukin 17A on left stellate ganglion remodeling are mediated by neuroimmune communication in normal structural hearts.

BACKGROUND: It is reported interleukin (IL)-17A, a classical proinflammatory cytokine, is implicated in neuroimmune-associated remodeling in neural plasticity and pathological conditions. However, the effect of IL-17A on left stellate ganglion (LSG) remodeling remains unclear. OBJECTIVE: This study was performed to determine whether exogenous IL-17A promotes LSG remodeling and destabilize ventricular electrophysiological properties (EPs) in normal canines. METHODS: 24 beagles were randomly allocated into three groups. In the first group, animals were subjected to 0.1 ml phosphate buffer saline (PBS) microinjection of into LSG (n = 8), an equivalent IL-17A was administrated in the second group (n = 8), and an equivalent anti-IL-17A mAb plus IL-17A was administrated in the third group (n = 8). The ventricular EPs, neural function and activity of the LSG were determined at baseline and 30 min after administration. In the end, LSG tissues were collected. RESULTS: Compared with the control group, the experimental group had a significantly shorter effective refractory period (ERP) and action potential duration (APD)90, an increased ERP, APD90, Smax dispersion, and APD alternans cycle length; and steepened APD restitution curves. In addition, IL-17A enhanced the neural function and activity of the LSG, upregulated the expressions of neuropeptides and proinflammatory cytokines and cells. And all these effects were attenuated by anti-IL-17A mAb. Importantly, IL-17 receptor A (IL-17R-A) was detected in sympathetic neurons in the LSG. CONCLUSION: IL-17A promoted LSG remodeling by regulating the neural inflammation response. It did so by binding to IL-17R-A, resulting in unstable ventricular electrophysiology in normal structural hearts.