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OBJECTIVES: The authors estimated changes of stressed blood volume (SBV) induced by splanchnic nerve block (SNB) in patients with either decompensated or ambulatory heart failure with reduced ejection fraction (HFrEF). BACKGROUND: The splanchnic vascular capacity is a major determinant of the SBV, which in turn determines cardiac filling pressures and may be modifiable through SNB. METHODS: We analyzed data from 2 prospective, single-arm clinical studies in decompensated HFrEF (splanchnic HF-1; resting hemodynamics) and ambulatory heart failure (splanchnic HF-2; exercise hemodynamics). Patients underwent invasive hemodynamics and short-term SNB with local anesthetics. SBV was simulated using heart rate, cardiac output, central venous pressure, pulmonary capillary wedge pressure, systolic and diastolic systemic arterial and pulmonary artery pressures, and left ventricular ejection fraction. SBV is presented as ml/70 kg body weight. RESULTS: Mean left ventricular ejection fraction was 21 ± 11%. In patients with decompensated HFrEF (n = 11), the mean estimated SBV was 3,073 ±251 ml/70 kg. At 30 min post-SNB, the estimated SBV decreased by 10% to 2,754 ± 386 ml/70 kg (p = 0.003). In ambulatory HFrEF (n = 14) patients, the mean estimated SBV was 2,664 ± 488 ml/70 kg and increased to 3,243 ± 444 ml/70 kg (p < 0.001) at peak exercise. The resting estimated SBV was lower in ambulatory patients with HFrEF than in decompensated HFrEF (p = 0.019). In ambulatory patients with HFrEF, post-SNB, the resting estimated SBV decreased by 532 ± 264 ml/70 kg (p < 0.001). Post-SNB, with exercise, there was no decrease of estimated SBV out of proportion to baseline effects (p = 0.661). CONCLUSIONS: The estimated SBV is higher in decompensated than in ambulatory heart failure. SNB reduced the estimated SBV in decompensated and ambulatory heart failure. The reduction in estimated SBV was maintained throughout exercise. (Splanchnic Nerve Anesthesia in Heart Failure, NCT02669407; Abdominal Nerve Blockade in Chronic Heart Failure, NCT03453151) (J Am Coll Cardiol HF 2021;9:293–300) © 2021 by the American College of Cardiology Foundation.

Traditional classification and prognostic approaches for chronic pain conditions focus primarily on anatomically based clinical characteristics not based on underlying biopsychosocial factors contributing to perception of clinical pain and future pain trajectories. Using a supervised clustering approach in a cohort of temporomandibular disorder cases and controls from the Orofacial Pain: Prospective Evaluation and Risk Assessment study, we recently developed and validated a rapid algorithm (ROPA) to pragmatically classify chronic pain patients into 3 groups that differed in clinical pain report, biopsychosocial profiles, functional limitations, and comorbid conditions. The present aim was to examine the generalizability of this clustering procedure in 2 additional cohorts: a cohort of patients with chronic overlapping pain conditions (Complex Persistent Pain Conditions study) and a real-world clinical population of patients seeking treatment at duke innovative pain therapies. In each cohort, we applied a ROPA for cluster prediction, which requires only 4 input variables: pressure pain threshold and anxiety, depression, and somatization scales. In both complex persistent pain condition and duke innovative pain therapies, we distinguished 3 clusters, including one with more severe clinical characteristics and psychological distress. We observed strong concordance with observed cluster solutions, indicating the ROPA method allows for reliable subtyping of clinical populations with minimal patient burden. The ROPA clustering algorithm represents a rapid and valid stratification tool independent of anatomic diagnosis. ROPA holds promise in classifying patients based on pathophysiological mechanisms rather than structural or anatomical diagnoses. As such, this method of classifying patients will facilitate personalized pain medicine for patients with chronic pain.

We hypothesized that splanchnic nerve blockade (SNB) would attenuate increased exercise-induced cardiac filling pressures in patients with chronic HF.Chronic heart failure (HF) is characterized by limited exercise capacity driven in part by an excessive elevation of cardiac filling pressures.This is a prospective, open-label, single-arm interventional study in chronic HF patients. Eligible patients had a wedge pressure ≥15 mm Hg at rest or ≥25 mm Hg with exercise on baseline right heart catheterization. Patients underwent cardiopulmonary exercise testing with invasive hemodynamic assessment, followed by percutaneous SNB with ropivacaine.Nineteen patients were enrolled, 15 of whom underwent SNB. The average age was 58 ± 13 years, 7 (47%) patients were women and 6 (40%) were black. Left ventricular ejection fraction was ≤35% in 14 (93%) patients. No procedural complications were encountered. SNB reduced mean pulmonary arterial pressure at peak exercise from 54.1 ± 14.4 (pre-SNB) to 45.8 ± 17.7 mm Hg (p 0.001) (post-SNB). Similarly, SNB reduced exercise-induced wedge pressure from 34.8 ± 10.0 (pre-SNB) to 25.1 ± 10.7 mm Hg (p 0.001) (post-SNB). The cardiac index changed with peak exercise from 3.4 ± 1.2 (pre-SNB) to 3.8 ± 1.1 l/min/mSNB reduced resting and exercise-induced pulmonary arterial and wedge pressure with favorable effects on cardiac output and exercise capacity. Continued efforts to investigate short- and long-term effects of SNB in chronic HF are warranted. Clinical Trials Registration (Abdominal Nerve Blockade in Chronic Heart Failure; NCT03453151).

PURPOSE OF REVIEW: To highlight the indications, procedural considerations, and data supporting the use of stellate ganglion blockade (SGB) for management of refractory ventricular arrhythmias. RECENT FINDINGS: In patients with refractory ventricular arrhythmias, unilateral or bilateral SGB can reduce arrhythmia burden and defibrillation events for 24–72 h, allowing time for use of other therapies like catheter ablation, surgical sympathectomy, or heart transplantation. The efficacy of SGB appears to be consistent despite the type (monomorphic vs polymorphic) or etiology (ischemic vs non-ischemic cardiomyopathy) of the ventricular arrhythmia. Ultrasound-guided SGB is safe with low risk for complications, even when performed on anticoagulation. SUMMARY: SGB is effective and safe and could be considered for patients with refractory ventricular arrhythmias.

This first-in-man proof-of-concept study tested a new therapeutic approach to the treatment of ADHF. This study supports the splanchnic nerve as a potential therapeutic target in ADHF.Thirteen patients were enrolled and 11 underwent the procedure.No procedural or haemodynamic complications were observed for48 h. The average age was 64± 13 years, 8 of 11 patients were maleand 6 of 11 were black. Ischaemic disease was present in sevenpatients. All patients had advanced systolic/diastolic HF with a leftventricular ejection fraction (LVEF) of an LVEF of 45% in one patient. Six patients were on inotropic agents(milrinone or dobutamine).Bilateral SNB resulted in temporary reduction of invasive haemodynamicssuch as mean PCWPs from 30± 7mmHg at baseline to22± 7mmHg at 30 min, P < 0.001 (Figure 1B). The cardiac indexincreased from 2.17 ± 0.74 L/min/m2 at baseline to 2.59 ± 0.65 L/min/m2 at 30min (P=0.007).Splanchnic nerve block temporarily reduced the cardiac sympathetictone as measured by heart rate variability parameters at 30minwithout significant changes at the end of the 90min (Figure 1C).Similar changes were observed for surrogate markers of the sympathetictone such as catecholamines. Following SNB, we observed atrend towards a decrease in central vascular pulse wave velocity, anindex of vascular stiffness and thoracic fluid content, measured withbioelectrance technology (Figure 1C).There was a decrease in mean left atrial volume index followingSNB (76 ± 23mL vs. 64 ± 12mL; P= 0.043) without changes in leftventricular size or diastolic function. Finally, patients reported anacute improvement in symptoms during the procedure (Figure 1D)and had an increase in average 6-min walk distance of 8.7± 51.6 m(range -115 to 71 m) from before to after the procedure (P=0.606)and 24.7± 31.2 m (range -28 to 71 m) 24 h after the procedure (P= 0.045).

The abdominal vascular compartment is the main storage of intravascular blood volume, and decreased abdominal vascular capacitance has been proposed as a major contributor to the complex pathophysiology of heart failure (HF) in animals and humans. 1, 2 In HF, as a result of neurohormonal imbalance, the vascular capacitance ("storage-space") is decreased and acute sympathetic nerve activation can result in acute volume redistribution 3 from the abdominal compartment to the thoracic compartment (heart and lungs), which increases intra-cardiac pressures and precipitates HF symptoms (Figure 1A). The sympathetic nervous system controls the splanchnic compartment via branches from the sympathetic thoracic ganglia (T6 through T11). 4 We have identified the splanchnic nerves as a potential target for treating HF.

Neuromodulation options that exist for chronic pain treatment include targeted intrathecal drug delivery, spinal cord stimulation, deep brain stimulation, cortical stimulation, and peripheral field stimulation. This chapter focuses on the neuromodulation technique of targeted intrathecal drug delivery. The chapter provides a brief overview of the history and focuses on clinically relevant discussion of patient selection, trialing, surgical technique, and other important topics for establishing a high-quality targeted intrathecal drug delivery program in this evolving age. The key to success with neuromodulation and targeted intrathecal drug delivery is patient selection. Appropriate pre-implantation screening and behavioral health assessment are critical. The choice of agent and route of delivery may play key roles in therapy success.

Introduction Treatment refractory ventricular arrhythmias (VAs) are often driven and exacerbated by heightened sympathetic tone. We aim to conduct a systematic review and meta-analysis of published studies of a temporary percutaneous stellate ganglion block (SGB) on VA burden and defibrillation episodes in patients with treatment refractory VAs. Methods Relevant studies from January 1960 through May 2017 were identified in PubMed and Google Scholar. We performed a patient-level analysis using Student's t-test to compare outcomes before and after SGB. Results We identified 22 unique case series with a total of 35 patients. Patients were 57 ± 17 years old and 69% were males with a high burden of VA. A unilateral (left)-sided SGB was used in 85.7% (30 of 35) of cases and the remaining were bilateral SGB. The use of a unilateral or bilateral SGB resulted in a significant reduction of VA episodes (24-hours pre: mean 16.5 [CI 9.7-23.1] events vs. post: mean 1.4 [CI 0.85-2.01] events; P = 0.0002) and need for defibrillation (24-hours pre: mean 14.2 [CI 6.8-21.6] vs. post: mean 0.6 [CI 0.3-0.9]; P = 0.0026). Furthermore, SGB was significantly associated with a reduction of VA burden regardless of etiology of cardiomyopathy, type of ventricular rhythm, and degree of contractile dysfunction. SGB was followed by surgical sympathectomy in 21% of cases. Conclusions Early experience suggests that SGB is associated with an acute reduction in the VA burden and offers potential promise for a broader use in high-risk populations. Randomized controlled studies are needed to confirm the safety and efficacy of this therapy.

Intrathecal catheter placement has long-term therapeutic benefits in the management of chronic, intractable pain. Despite the diverse clinical applicability and rising prevalence of implantable drug delivery systems in pain medicine, the spectrum of complications associated with intrathecal catheterization remains largely understudied and underreported in the literature.To report a case of thoracic nerve root entrapment resulting from intrathecal catheter migration.Case report.Inpatient hospital service.A 60-year-old man status post implanted intrathecal (IT) catheter for intractable low back pain secondary to failed back surgery syndrome returned to the operating room for removal of IT pump trial catheter after experiencing relapse of preoperative pain and pump occlusion. Initial attempt at ambulatory removal of the catheter was aborted after the patient reported acute onset of lower extremity radiculopathic pain during the extraction. Noncontrast computed tomography (CT) subsequently revealed that the catheter had ascended and coiled around the T10 nerve root. The patient was taken back to the operating room for removal of the catheter under fluoroscopic guidance, with possible laminectomy for direct visualization. Removal was ultimately achieved with slow continuous tension, with complete resolution of the patient's new radicular symptoms.This report describes a single case report.This case demonstrates that any existing loops in the intrathecal catheter during initial implantation should be immediately re-addressed, as they can precipitate nerve root entrapment and irritation. Reduction of the loop or extrication of the catheter should be attempted under continuous fluoroscopic guidance to prevent further neurosurgical morbidity.

This case discusses a synergistic pharmacodynamic interaction between morphine and bupivacaine, resulting in death. This drug pair eliminated both central and peripheral respiratory drive.

PURPOSE: Implantable intrathecal drug delivery systems (IDDSs) have been used to manage refractory cancer pain, but there are no randomized clinical trial (RCT) data comparing them with comprehensive medical management (CMM). PATIENTS AND METHODS: We enrolled 202 patients on an RCT of CMM versus IDDS plus CMM. Entry criteria included unrelieved pain (visual analog scale [VAS] pain scores ≥ 5 on a 0 to 10 scale). Clinical success was defined as ≥ 20% reduction in VAS scores, or equal scores with ≥ 20% reduction in toxicity. The main outcome measure was pain control combined with change of toxicity, as measured by the National Cancer Institute Common Toxicity Criteria, 4 weeks after randomization. RESULTS: Sixty of 71 IDDS patients (84.5%) achieved clinical success compared with 51 of 72 CMM patients (70.8%, P = .05). IDDS patients more often achieved ≥ 20% reduction in both pain VAS and toxicity (57.7% [41 of 71] v 37.5% [27 of 72], P = .02). The mean CMM VAS score fell from 7.81 to 4.76 (39% reduction); for the IDDS group, the scores fell from 7.57 to 3.67 (52% reduction, P = .055). The mean CMM toxicity scores fell from 6.36 to 5.27 (17% reduction); for the IDDS group, the toxicity scores fell from 7.22 to 3.59 (50% reduction, P = .004). The IDDS group had significant reductions in fatigue and depressed level of consciousness (P < .05). IDDS patients had improved survival, with 53.9% alive at 6 months compared with 37.2% of the CMM group (P = .06). CONCLUSION: IDDSs improved clinical success in pain control, reduced pain, significantly relieved common drug toxicities, and improved survival in patients with refractory cancer pain.

Preclinical studies suggest that endogenous opioids and/or opioid medications may contribute to tumor growth. However, endogenous and exogenous opioids have not been modulated over time in cancer patients, who often need opioids for pain control. Most of the analgesic effect of opioids occurs through the activation of the μ-opioid receptor. The most common naturally occurring genetic variation of this receptor in humans is the so-called A118G mutation. Individuals with this mutation have been shown to have a reduced analgesic response to opioid medications. In a recent study, we used this naturally occurring genetic variation to look for evidence that endogenous and/or exogenous opioids influence tumor growth in humans. We hypothesized that if opioids do influence tumor growth, then cancer patients with the A118G mutation, as a group, should have longer survivals than those without it. Using data from the Carolina Breast Cancer Study, we found that, among 2,039 women diagnosed with breast cancer, the presence of A118G was associated with longer breast cancer specific survival. The protective effect of A118G was limited to invasive cases only and appeared to increase with the stage of cancer at diagnosis. This study did not assess whether opioid pain medications have any influence on cancer mortality. Moreover, the study was performed in African Americans and European Americans only, and requires replication.

Objectives: The aim of this study was to evaluate the safety and efficacy of spinal cord stimulation (SCS) for refractory angina. Materials and Methods: This multicenter, randomized, single-blind, controlled trial evaluated SCS in two patient groups: high stimulation (HS) (treatment) and low stimulation (LS) (control). The HS group controlled SCS with a programmer for a minimum of two hours four times daily. The LS group received SCS therapy above the paresthesia threshold for one min once daily. The primary efficacy endpoint was number of angina attacks recorded by patients at six months. The primary safety endpoint was the major adverse cardiac event (MACE) rate at six months. Results: Due to slow enrollment, a futility analysis was performed, resulting in early termination of the study. Sixty-eight patients were randomized after implantation. Mean change in angina attacks per day from baseline to six months was −1.19 ± 2.13 (HS) and −1.29 ± 1.66 (LS). The difference from baseline was significant within each group (both p

Background Preclinical studies suggest that opioids may promote tumor growth. Genetic polymorphisms have been shown to affect opioid receptor function and to modify the clinical effects of morphine. In this study we assessed the association between six common polymorphisms in the μ-opioid receptor gene, including the well known A118G polymorphism, and breast cancer survival. Methods A total of 2,039 women ages 23-74 yr (38% African-American, 62% European-American, 55% postmenopausal) diagnosed with breast cancer between 1993-2001 were followed through 2006. Genotyping was performed using the TaqMan platform (Applied Biosystems Inc., Foster City, CA). Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models were used to examine the association between each genotype and survival. Results After Bonferroni correction for multiple testing, patient genotype at A118G was associated with breast cancer-specific mortality at 10 yr. Women with one or more copies of the G allele had decreased breast cancer-specific mortality (P < 0.001). This association was limited to invasive cases only; effect size appeared to increase with clinical stage. Cox regression model adjusted for age and ethnicity also showed decreased mortality in A/G and G/G genotypes compared with A/A genotype (hazard ratio = 0.57 [0.38, 0.85] and 0.32 [0.22, 0.49], respectively; P = 0.006). Conclusions These results suggest that opioid pathways may be involved in tumor growth. Further studies examining the association between genetic variants influencing opioid system function and cancer survival are warranted.

Background: The randomized clinical trial of implantable drug delivery systems (IDDS) plus comprehensive medical management (CMM) versus CMM alone showed better clinical success at 4 weeks for IDDS patients. This ‘as treated’ analysis assessed if improvements in pain control, drug toxicity and survival were maintained over time. Patients and methods: We compared those who received IDDS with those who did not receive IDDS (non-IDDS). All patients had Visual Analogue Scores (VAS) for pain > _ 5/10 on at least 200 mg morphine or equivalent daily. Results: At 4 weeks, 46 of 52 (88.5%) IDDS patients achieved clinical success compared with 65 of 91 (71.4%; P = 0.02) non-IDDS patients, and more often achieved > _ 20% reduction in both pain VAS and toxicity [35 of 52 (67.3%) versus 33 of 91 patients (36.3%); P = 0.0003]. By 12 weeks, 47 of 57 (82.5%) IDDS patients had clinical success compared with 35 of 45 (77.8%; P = 0.55) nonIDDS patients, and more often had a > 20% reduction in both pain VAS and toxicity [33 of 57 (57.9%) versus 15 of 45 patients (33.3%); P = 0.01]. At 12 weeks the IDDS VAS pain scores decreased from 7.81 to 3.89 (47% reduction) compared with 7.21 to 4.53 for non-IDDS patients (42% reduction; P = 0.23). The 12 week drug toxicity scores for IDDS patients decreased from 6.68 to 2.30 (66% reduction), and for non-IDDS patients from 6.73 to 4.13 (37% reduction; P = 0.01). All individual drug toxicities improved with IDDS at both 4 and 12 weeks. At 6 months, only 32% of the group randomized to CMM and who did not cross over to IDDS were alive, compared with 52% – 59% for patients in those groups who received IDDS. Conclusions: IDDS improved clinical success, reduced pain scores, relieved most toxicity of pain control drugs, and was associated with increased survival for the duration of this 6 month trial.

Background There is limited neuropathologic information available from cases of Sneddon’s syndrome in which strokes are associated with livedo reticularis. Pathogenesis of the syndrome is controversial, although current opinion favors a coagulopathy, often with antiphospholipid antibodies. We describe a case lacking antiphospholipid antibodies but having a granulomatous infiltration of the leptomeninges. Case Description The patient presented at age 29 with stroke, livedo reticularis, essential hypertension, and Raynaud’s phenomenon. Assessment uncovered no underlying disease, including absent antiphospholipid antibodies. A leptomeningeal biopsy showed granulomatous infiltration. Conclusions The findings suggest that an inflammatory process plays a role in at least some cases of Sneddon’s syndrome.

This study examined the effects of 365 occurrences on the intracranial pressure (ICP) of four patients with severe head injuries and a Glasgow Coma Score below five. The occurrences were in: 1) health care activities, 2) patient-initiated activities, and 3) environmental stimuli. The health care activities that increased intracranial pressure were suctioning, turning, and flexion of the head; decreases were realized by elevating the head of the bed and repositioning the patient. The patient-initiated activities that increased intracranial pressure were flexion of extremities, rotation of the neck, and coughing. In contrast to previous reports, environmental stimuli did not affect intracranial pressure and bathing increased it. Recommendations for nursing care include: turning patients more slowly to less acute angles; proper head/neck positioning; and more direct psychosocial interactions with families of patients who have low Glasgow Coma Scores.