Complex Regional Pain Syndrome: Evidence-Based Advances in Concepts and Treatments.

PURPOSE OF REVIEW: This review presents the most current information about the epidemiology of complex regional pain syndrome (CRPS), classification and diagnostic criteria, childhood CRPS, subtypes, pathophysiology, conventional and less conventional treatments, and preventive strategies. RECENT FINDINGS: CRPS is a painful disorder with multifactorial pathophysiology. The data describe sensitization of the central and peripheral nervous systems, inflammation, possible genetic factors, sympatho-afferent coupling, autoimmunity, and mental health factors as contributors to the syndrome. In addition to conventional subtypes (type I and type II), cluster analyses have uncovered other proposed subtypes. Prevalence of CRPS is approximately 1.2%, female gender is consistently associated with a higher risk of development, and substantial physical, emotional, and financial costs can result from the syndrome. Children with CRPS seem to benefit from multifaceted physical therapy leading to a high percentage of symptom-free patients. The best available evidence along with standard clinical practice supports pharmacological agents, physical and occupational therapy, sympathetic blocks for engaging physical restoration, steroids for acute CRPS, neuromodulation, ketamine, and intrathecal baclofen as therapeutic approaches. There are many emerging treatments that can be considered as a part of individualized, patient-centered care. Vitamin C may be preventive. CRPS can lead to progressively painful sensory and vascular changes, edema, limb weakness, and trophic disturbances, all of which substantially erode healthy living. Despite some progress in research, more comprehensive basic science investigation is needed to clarify the molecular mechanisms of the disease so that targeted treatments can be developed for better outcomes. Incorporating a variety of standard therapies with different modes of action may offer the most effective analgesia. Introducing less conventional approaches may also be helpful when traditional treatments fail to provide sufficient improvement.

A survey of pain physicians: Needlesticks injuries.

OBJECTIVE: To investigate and characterize the incidence of needlestick injuries (NSI) in a sample of practicing pain medicine physicians, with the ultimate goal of aiding to prevent these injuries by raising awareness of their prevalence. DESIGN: A cross-sectional research survey. SETTING: A REDCap survey was emailed to physicians who had membership to the American Academy of Pain Medicine. SUBJECTS: Eligibility criteria included physicians who were actively practicing and identified as pain physicians who participated in procedures with needlesticks or sharps. METHODS: Basic demographics without identifiers were collected, including practice setting, years in practice, and training type. Respondents were asked to estimate the number of sharps-involved procedure days per week and per day. They were then asked to estimate the number of NSIs they sustained since completing training and in the past year. RESULTS: A total of 430 surveys were opened by email by potential participants, of which 124 responded (response rate 29%). Data from a total of 109 respondents that met inclusion criteria were included. Roughly 60% of respondents reported at least one NSI since completing training and approximately one-third had sustained more than three NSIs. In the last year, roughly 19% of providers reported at least one needlestick injury. The number of NSIs reported by providers since completing training was not significantly associated with practice setting, the number of procedure days per week, or the number of sharps-involved procedures per day. There was a significant relationship between years post-training and number of NSIs since completing training, with providers with more years post-training reporting higher incidences of NSIs (p < 0.0005). The number of NSIs since completing training and the number of NSIs were also associated, with providers that had sustained a greater number of total NSIs reporting a higher incidence of NSIs within the last year (p < 0.0005). CONCLUSIONS: This study characterizes NSIs in a population of pain medicine physicians. These data warrant caution and will hopefully raise awareness amongst providers.

Peripheral Nerve Stimulation for Chronic Pain and Migraine: A Review.

Interventional pain procedures offer treatments for chronic pain conditions refractory to conservative measures. Neuromodulation, including peripheral nerve stimulation (PNS), applies electrical stimuli to neural structures to treat pain. Here we review the literature on PNS for various chronic pain conditions including neuropathic pain, postamputation pain, musculoskeletal pain, migraine, and pelvic pain.

Electronic and Tobacco Cigarettes Alter Polyunsaturated Fatty Acids and Oxidative Biomarkers.

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Disinfectants In Interventional Practices.

PURPOSE OF REVIEW: This review aims to provide relevant, aggregate information about a variety of disinfectants and antiseptics, along with potential utility and limitations. While not exhaustive, this review's goal is to add to the body of literature available on this topic and give interventional providers and practitioners an additional resource to consider when performing procedures. RECENT FINDINGS: In the current SARS-CoV2 epidemiological environment, infection control and costs associated with healthcare-associated infections (HAIs) are of paramount importance. Even before the onset of SARS-CoV2, HAIs affected nearly 2million patients a year in the USA and resulted in nearly 90,000 deaths, all of which resulted in a cost to hospitals ranging from US$28 billion to 45 billion. The onset SARS-CoV2, though not spread by an airborne route, has heightened infection control protocols in hospitals and, as such, cast a renewed focus on disinfectants and their utility across different settings and organisms. The aim of this review is to provide a comprehensive overview of disinfectants used in the inpatient setting.

Differential effects of tobacco cigarettes and electronic cigarettes on endothelial function in healthy young people.

Tobacco cigarette (TC) smoking has never been lower in the United States, but electronic cigarette (EC) vaping has reached epidemic proportions among our youth. Endothelial dysfunction, as measured by flow-mediated vasodilation (FMD) is a predictor of future atherosclerosis and adverse cardiovascular events and is impaired in young TC smokers, but whether FMD is also reduced in young EC vapers is uncertain. The aim of this study in otherwise healthy young people was to compare the effects of acute and chronic tobacco cigarette (TC) smoking and electronic cigarette (EC) vaping on FMD. FMD was compared in 47 nonsmokers (NS), 49 chronic EC vapers, and 40 chronic TC smokers at baseline and then after EC vapers (n = 31) and nonsmokers (n = 47) acutely used an EC with nicotine (ECN), EC without nicotine (EC0), and nicotine inhaler (NI) at ~4-wk intervals and after TC smokers (n = 33) acutely smoked a TC, compared with sham control. Mean age (NS, 26.3 ± 5.2 vs. EC, 27.4 ± 5.45 vs. TC, 27.1 ± 5.51 yr, P = 0.53) was similar among the groups, but there were more female nonsmokers. Baseline FMD was not different among the groups (NS, 7.7 ± 4.5 vs. EC:6.6 ± 3.6 vs. TC, 7.9 ± 3.7%∆, P = 0.35), even when compared by group and sex. Acute TC smoking versus control impaired FMD (FMD pre-/postsmoking, -2.52 ± 0.92 vs. 0.65 ± 0.93%∆, P = 0.02). Although the increase in plasma nicotine was similar after EC vapers used the ECN versus TC smokers smoked the TC (5.75 ± 0.74 vs. 5.88 ± 0.69 ng/mL, P = 0.47), acute EC vaping did not impair FMD. In otherwise healthy young people who regularly smoke TCs or ECs, impaired FMD compared with that in nonsmokers was not present at baseline. However, FMD was significantly impaired after smoking one TC, but not after vaping an equivalent "dose" (estimated by change in plasma nicotine) of an EC, consistent with the notion that non-nicotine constituents in TC smoke mediate the impairment. Although it is reassuring that acute EC vaping did not acutely impair FMD, it would be dangerous and premature to conclude that ECs do not lead to atherosclerosis.NEW & NOTEWORTHY In our study of otherwise healthy young people, baseline flow-mediated dilation (FMD), a predictor of atherosclerosis and increased cardiovascular risk, was not different among tobacco cigarette (TC) smokers or electronic cigarette (EC) vapers who had refrained from smoking, compared with nonsmokers. However, acutely smoking one TC impaired FMD in smokers, whereas vaping a similar EC "dose" (as estimated by change in plasma nicotine levels) did not. Finally, although it is reassuring that acute EC vaping did not acutely impair FMD, it would be premature and dangerous to conclude that ECs do not lead to atherosclerosis or increase cardiovascular risk.

Acute and chronic sympathomimetic effects of e-cigarette and tobacco cigarette smoking: role of nicotine and non-nicotine constituents.

Electronic cigarettes (ECs) and tobacco cigarettes (TCs) both release nicotine, a sympathomimetic drug. We hypothesized that baseline heart rate variability (HRV) and hemodynamics would be similar in chronic EC and TC smokers and that after acute EC use, changes in HRV and hemodynamics would be attributable to nicotine, not non-nicotine, constituents in EC aerosol. In 100 smokers, including 58 chronic EC users and 42 TC smokers, baseline HRV and hemodynamics [blood pressure (BP) and heart rate (HR)] were compared. To isolate the acute effects of nicotine vs. non-nicotine constituents in EC aerosol, we compared changes in HRV, BP, and HR in EC users after using an EC with nicotine (ECN), EC without nicotine (EC0), nicotine inhaler (NI), or sham vaping (control). Outcomes were also compared with TC smokers after smoking one TC. Baseline HRV and hemodynamics were not different in chronic EC users and TC smokers. In EC users, BP and HR, but not HRV outcomes, increased only after using the ECN, consistent with a nicotine effect on BP and HR. Similarly, in TC smokers, BP and HR but not HRV outcomes increased after smoking one TC. Despite a similar increase in nicotine, the hemodynamic increases were significantly greater after TC smokers smoked one TC compared with the increases after EC users used the ECN. In conclusion, chronic EC and TC smokers exhibit a similar pattern of baseline HRV. Acute increases in BP and HR in EC users are attributable to nicotine, not non-nicotine, constituents in EC aerosol. The greater acute pressor effects after TC compared with ECN may be attributable to non-nicotine, combusted constituents in TC smoke.NEW & NOTEWORTHY Chronic electronic cigarette (EC) users and tobacco cigarette (TC) smokers exhibit a similar level of sympathetic nerve activity as estimated by heart rate variability. Acute increases in blood pressure (BP) and heart rate in EC users are attribute to nicotine, not non-nicotine, constituents in EC aerosol. Acute TC smoking increased BP significantly more than acute EC use, despite similar increases in plasma nicotine, suggestive of additional adverse vascular effects attributable to combusted, non-nicotine constituents in TC smoke.

Tobacco and electronic cigarettes adversely impact ECG indexes of ventricular repolarization: implication for sudden death risk.

Tobacco cigarette smoking is associated with increased sudden death risk, perhaps through adverse effects on ventricular repolarization. The effect of electronic (e-)cigarettes on ventricular repolarization is unknown. The objective of the study was to test the hypothesis that tobacco cigarettes and e-cigarettes have similar adverse effects on electrocardiogram (ECG) indexes of ventricular repolarization and these effects are attributable to nicotine. ECG recordings were obtained in 37 chronic tobacco cigarette smokers, 43 chronic e-cigarette users, and 65 nonusers. Primary outcomes, Tpeak to Tend (Tp-e), Tp-e/QT ratio, and Tp-e/QTc ratio, were measured in tobacco cigarette smokers pre-/post-straw control and smoking one tobacco cigarette and in e-cigarette users and nonusers pre-/post-straw control and using an e-cigarette with and without nicotine (different days). Mean values of the primary outcomes were not different among the three groups at baseline. In chronic tobacco cigarette smokers, all primary outcomes, including the Tp-e (12.9 ± 5.0% vs. 1.5 ± 5%, P = 0.017), Tp-e/QT (14.9 ± 5.0% vs. 0.7 ± 5.1%, P = 0.004), and Tp-e/QTc (11.9 ± 5.0% vs. 2.1 ± 5.1%, P = 0.036), were significantly increased pre-/post-smoking one tobacco cigarette compared with pre-/post-straw control. In chronic e-cigarette users, the Tp-e/QT (6.3 ± 1.9%, P = 0.046) was increased only pre/post using an e-cigarette with nicotine but not pre/post the other exposures. The changes relative to the changes after straw control were greater after smoking the tobacco cigarette compared with using the e-cigarette with nicotine for Tp-e (11.4 ± 4.4% vs. 1.1 ± 2.5%, P < 0.05) and Tp-e/QTc (9.8 ± 4.4% vs. -1.6 ± 2.6%, P = 0.05) but not Tp-e/QT(14.2 ± 4.5% vs. 4.2 ± 2.6%, P = 0.061) . Heart rate increased similarly after the tobacco cigarette and e-cigarette with nicotine. Baseline ECG indexes of ventricular repolarization were not different among chronic tobacco cigarette smokers, electronic cigarette users and nonusers. An adverse effect of acute tobacco cigarette smoking on ECG indexes of ventricular repolarization was confirmed. In chronic e-cigarette users, an adverse effect of using an e-cigarette with nicotine, but not without nicotine, on ECG indexes of ventricular repolarization was also observed.NEW & NOTEWORTHY Abnormal ventricular repolarization, as indicated by prolonged Tpeak-end (Tp-e), is associated with increased sudden death risk. Baseline ECG indexes of repolarization, Tp-e, Tp-e/QT, and Tp-e/QTc, were not different among tobacco cigarette (TC) smokers, electronic cigarette (EC) users, and nonsmokers at baseline, but when TC smokers smoked one TC, all parameters were prolonged. Using an electronic cigarette with nicotine, but not without nicotine, increased the Tp-e/QT. Smoking induces changes in ECG indexes of ventricular repolarization associated with increased sudden death risk.

A Review of Clinical Data on Salvage Therapy in Spinal Cord Stimulation.

BACKGROUND: Since its introduction in 1967, neuromodulation through spinal cord stimulation (SCS) or dorsal root ganglion stimulation (DRGs) has advanced significantly in both the technology and indications for use. There are now over 14,000 SCS implants performed worldwide every year. This review focuses on mechanisms behind the loss of efficacy in neuromodulation and current data on salvage therapy, defined as the conversion of a neuromodulation device to an alternative SCS or DRG stimulation, in the event of loss of efficacy or failure of a trial. STUDY DESIGN: A narrative review of clinical studies regarding habituation, explant data, and salvage therapy with SCS. METHODS: Available literature was reviewed on spinal cord stimulation technology and salvage therapy. Data sources included relevant literature identified through searches of PubMed, MEDLINE/OVID, SCOPUS, and manual searches of the bibliographies of known primary and review articles. OUTCOME MEASURES: The primary outcome measures were to understand the mechanisms of loss of efficacy, provide a review of explants due to failure in treatment, and summarize the data on current salvage therapy in SCS. RESULTS: A total of eight studies and four abstracts/poster presentations were identified and reviewed. Of the eight studies, only one was a randomized controlled trial. CONCLUSIONS: There is limited evidence for the appropriate treatment alternatives, but from data currently available the conversion from conventional tonic stimulation to burst, high frequency (10 kHz), multiple wave forms, and/or DRGs may be appropriate in select patients and will require further research to determine the most appropriate first line salvage in the context of the underlying pain pathology.

Management of an Acute Exacerbation of Chronic Neuropathic Pain in the Emergency Department: A Case to Support Ultrasound-Guided Forearm Nerve Blocks.

BACKGROUND: Acute on chronic neuropathic pain is often refractory to analgesics and can be challenging to treat in the emergency department (ED). In addition, systemic medications such as opiates and nonsteroidal inflammatory drugs have risks, including hypotension and kidney injury, respectively. Difficulties in managing pain in patients with neuropathy can lead to prolonged ED stays, undesired admissions, and subsequent increased health care costs. CASE REPORT: We describe the case of a 51-year-old woman who presented to the ED on two separate occasions for left forearm pain secondary to chronic ulnar neuropathy. During her first ED visit, the patient received multiple rounds of intravenous opiates and required hospital admission, which was complicated by opiate-induced hypotension. During her second visit, she underwent an ultrasound-guided ulnar nerve block performed by the emergency physician; her pain resolved and she was discharged home. WHY SHOULD EMERGENCY PHYSICIANS BE AWARE OF THIS?: Ultrasound-guided nerve blocks are an effective, safe, and relatively inexpensive alternative to opioids. Our case demonstrates that emergency providers may be able to perform ultrasound-guided regional anesthesia to treat an acute exacerbation of chronic neuropathic pain.

Sympathomimetic Effects of Acute E-Cigarette Use: Role of Nicotine and Non-Nicotine Constituents.

BACKGROUND: Chronic electronic (e) cigarette users have increased resting cardiac sympathetic nerve activity and increased susceptibility to oxidative stress. The purpose of the present study is to determine the role of nicotine versus non-nicotine constituents in e-cigarette emissions in causing these pathologies in otherwise healthy humans. METHODS AND RESULTS: Thirty-three healthy volunteers who were not current e-cigarette or tobacco cigarette smokers were studied. On different days, each participant used an e-cigarette with nicotine, an e-cigarette without nicotine, or a sham control. Cardiac sympathetic nerve activity was determined by heart rate variability, and susceptibility to oxidative stress was determined by plasma paraoxonase activity. Following exposure to the e-cigarette with nicotine, but not to the e-cigarette without nicotine or the sham control, there was a significant and marked shift in cardiac sympathovagal balance towards sympathetic predominance. The decrease in high-frequency component and the increases in the low-frequency component and the low-frequency to high-frequency ratio were significantly greater following exposure to the e-cigarette with nicotine compared with exposure to the e-cigarette without nicotine or to sham control. Oxidative stress, as estimated by plasma paraoxonase, did not increase following any of the 3 exposures. CONCLUSIONS: The acute sympathomimetic effect of e-cigarettes is attributable to the inhaled nicotine, not to non-nicotine constituents in e-cigarette aerosol, recapitulating the same heart rate variability pattern associated with increased cardiac risk in multiple populations with and without known cardiac disease. Evidence of oxidative stress, as estimated by plasma paraoxonase activity, was not uncovered following acute e-cigarette exposure.

Activation of the "Splenocardiac Axis" by electronic and tobacco cigarettes in otherwise healthy young adults.

The "Splenocardiac Axis" describes an inflammatory signaling network underlying acute cardiac ischemia, characterized by sympathetic nerve stimulation of hematopoietic tissues, such as the bone marrow and spleen, which then release proinflammatory monocytes that populate atherosclerotic plaques, thereby promoting ischemic heart disease. Electronic (e) cigarettes, like tobacco cigarettes trigger sympathetic nerve activation, but virtually nothing is known about their influence on hematopoietic and vascular tissues and cardiovascular risks. The objective of this study was to determine if the Splenocardiac Axis is activated in young adults who habitually use either tobacco or e-cigarettes. In otherwise healthy humans who habitually use tobacco cigarettes or e-cigarettes (not both), we used 18F-flurorodeoxyglucose positron emission tomography/computer tomography (FDG-PET/CT) to test the hypothesis that tobacco or e-cigarettes increased metabolic activity of the hematopoietic and vascular tissues. FDG uptake in the spleen increased from nonuser controls (1.62 ± 0.07), to the e-cigarette users (1.73 ± 0.04), and was highest in tobacco cigarette smokers (1.82 ± 0.09; monotone P = 0.05). Similarly, FDG uptake in the aorta increased from the nonuser controls (1.87 ± 0.07) to the e-cigarette users (1.98 ± 0.07), and was highest in tobacco cigarette smokers (2.10 ± 0.07; monotone P = 0.04). FDG uptake in the skeletal muscle, which served as a control tissue, was not different between the groups. In conclusion, these findings are consistent with activation of the Splenocardiac Axis by emissions from tobacco cigarettes and e-cigarettes. This activation suggests a mechanism by which tobacco cigarettes, and potentially e-cigarettes, may lead to increased risk of future cardiovascular events.

Increased Cardiac Sympathetic Activity and Oxidative Stress in Habitual Electronic Cigarette Users: Implications for Cardiovascular Risk.

Importance: Electronic cigarettes (e-cigarettes) have gained unprecedented popularity, but virtually nothing is known about their cardiovascular risks. Objective: To test the hypothesis that an imbalance of cardiac autonomic tone and increased systemic oxidative stress and inflammation are detectable in otherwise healthy humans who habitually use e-cigarettes. Design, Setting, and Participants: Cross-sectional case-control study of habitual e-cigarette users and nonuser control individuals from 2015 to 2016 at the University of California, Los Angeles. Otherwise healthy habitual e-cigarette users between the ages of 21 and 45 years meeting study criteria, including no current tobacco cigarette smoking and no known health problems or prescription medications, were eligible for enrollment. Healthy volunteers meeting these inclusion criteria who were not e-cigarette users were eligible to be enrolled as control individuals. A total of 42 participants meeting these criteria were enrolled in the study including 23 self-identified habitual e-cigarette users and 19 self-identified non-tobacco cigarette, non-e-cigarette user control participants. Main Outcomes and Measures: Heart rate variability components were analyzed for the high-frequency component (0.15-0.4 Hz), an indicator of vagal activity, the low-frequency component (0.04-0.15 Hz), a mixture of both vagal and sympathetic activity, and the ratio of the low frequency to high frequency, reflecting the cardiac sympathovagal balance. Three parameters of oxidative stress were measured in plasma: (1) low-density lipoprotein oxidizability, (2) high-density lipoprotein antioxidant/anti-inflammatory capacity, and (3) paraoxonase-1 activity. Results: Of the 42 participants, 35% were women, 35% were white, and the mean age was 27.6 years. The high-frequency component was significantly decreased in the e-cigarette users compared with nonuser control participants (mean [SEM], 46.5 [3.7] nu vs 57.8 [3.6] nu; P = .04). The low-frequency component (mean [SEM], 52.7 [4.0] nu vs 39.9 [3.8] nu; P = .03) and the low frequency to high frequency ratio (mean [SEM], 1.37 [0.19] vs 0.85 [0.18]; P = .05) were significantly increased in the e-cigarette users compared with nonuser control participants, consistent with sympathetic predominance. Low-density lipoprotein oxidizability, indicative of the susceptibility of apolipoprotein B-containing lipoproteins to oxidation, was significantly increased in e-cigarette users compared with nonuser control individuals (mean [SEM], 3801.0 [415.7] U vs 2413.3 [325.0] U; P = .01) consistent with increased oxidative stress, but differences in high-density antioxidant/anti-inflammatory capacity and paraoxonase-1 activity were not significant. Conclusions and Relevance: In this study, habitual e-cigarette use was associated with a shift in cardiac autonomic balance toward sympathetic predominance and increased oxidative stress, both associated with increased cardiovascular risk.

Emergency Physicians' Perceptions and Decision-making Processes Regarding Patients Presenting with Palpitations.

BACKGROUND: Palpitations are a common emergency department (ED) complaint, yet relatively little research exists on this topic from an emergency care perspective. OBJECTIVES: We sought to describe the perceptions and clinical decision-making processes of emergency physicians (EP) surrounding patients with palpitations. METHODS: We conducted 21 semistructured interviews with a convenience sample of EPs. We recruited participants from academic and community practice settings from four regions of the United States. The transcribed interviews were analyzed using a combination of structural coding and grounded theory approaches with ATLAS.ti, a qualitative data analysis software program (version 7; Atlas.ti Scientific Software Development GmbH, Berlin, Germany). RESULTS: EPs perceive palpitations to be a common but generally benign chief complaint. EPs' clinical approach to palpitations, with regards to testing, treatment, and ED management, can be classified as relating to one or more of the following themes: (1) risk stratification, (2) diagnostic categorization, (3) algorithmic management, and (4) case-specific gestalt. With regard to disposition decisions, four main themes emerged: (1) presence of a serious diagnosis, (2) perceived need for further cardiac testing/monitoring, (3) presence of key associated symptoms, (4) request of other physician or patient desire. The interrater reliability exercise yielded a Fleiss' kappa measure of 0.69, indicating substantial agreement between coders. CONCLUSION: EPs perceive palpitations to be a common but generally benign chief complaint. EPs rely on one or more of four main clinical approaches to manage these patients. These findings could help guide future efforts at developing risk-stratification tools and clinical algorithms for patients with palpitations.

Adverse effects of cigarette and noncigarette smoke exposure on the autonomic nervous system: mechanisms and implications for cardiovascular risk.

This review summarizes the detrimental effects of cigarette and noncigarette emission exposure on autonomic function, with particular emphasis on the mechanisms of acute and chronic modulation of the sympathetic nervous system. We propose that the nicotine and fine particulate matter in tobacco smoke lead to increased sympathetic nerve activity, which becomes persistent via a positive feedback loop between sympathetic nerve activity and reactive oxidative species. Furthermore, we propose that baroreflex suppression of sympathetic activation is attenuated in habitual smokers; that is, the baroreflex plays a permissive role, allowing sympathoexcitation to occur without restraint in the setting of increased pressor response. This model is also applicable to other nontobacco cigarette emission exposures (e.g., marijuana, waterpipes [hookahs], electronic cigarettes, and even air pollution). Fortunately, emerging data suggest that baroreflex sensitivity and autonomic function may be restored after smoking cessation, providing further evidence in support of the health benefits of smoking cessation.