Vascular Pain Research Articles

12. Vascular pain: Ischemic pain in the extremities and Raynaud's syndrome

Peripheral artery diseases (PAD) and Raynaud's syndrome are associated with substantial morbidity. PAD, through the restriction of blood flow to the extremities, may lead to critical limb ischemia with symptoms of pain at rest which may eventually progress to severe limb ischemia with gangrene. This serious and painful clinical condition requires extensive medical care, is limb-threatening and, in case of delayed or unsuccessful treatment, is associated with a high mortality rate. In Raynaud's syndrome, the blood supply to certain parts of the body, usually the fingers and toes and less frequently the nose or ears, is restricted because of vasculopathy of the smaller vessels at acral sites. Under certain circumstances, with cold as the most well-known provoking factor, blood flow restriction occurs, leading to demarcated color changes and symptoms such as pain, paresthesia, and numbness. In severe cases of Raynaud syndrome tissue ischemia may lead to necrosis and the need for amputation of the affected area. In this narrative review, the literature on the diagnosis and interventional pain treatment of PAD and Raynaud's syndrome was updated and summarized. This review focused on interventional pain treatment. In PAD, the effects of the intervention on limb salvage, ulcer healing, and ischemic pain were summarized. Additionally, results with respect to skin microcirculation and quality of life were reported if available. In Raynaud's syndrome, we focused on the effect of the intervention on peripheral blood flow metrics and pain intensity during attacks. In PAD, prevention and treatment of risk factors are important. Initially, conservative treatment and pharmacological therapy are preferred first-line therapies. However, when disease progression occurs, interventional management may be considered. The literature search yielded conflicting evidence for sympathectomy as a treatment for PAD. Spinal cord stimulation (SCS) as a treatment modality for advanced PAD had high-quality evidence for limb salvage in subgroups of patients but conflicting evidence for other outcome measures such as pain, wound healing, and quality of life. The literature search for interventional pain management in Raynaud's syndrome was limited to only one randomized controlled trial (RCT) studying the effect of thoracic sympathectomy. This study had several limitations and hence the level of evidence for this interventional treatment is very low. No RCTs studying SCS in patients with Raynaud's syndrome were found. In both PAD and Raynaud's syndrome, additional RCTs are needed to substantiate interventional (pain) management and bolster the evidence base for sympathectomy and SCS as treatment options.

FORMULATION OPTIMIZATION AND CHARACTERIZATION OF NEWSTABLE READY TO USE (RTU) INJECTABLE FORMULATION OF ROCURONIUM BROMIDE

Commercially available injectable Rocuronium Bromide, a non-depolarizing neuromuscular blocker intended to store in a refrigerator at 2-8°C, requires an additional storage facility. The primary objectives of the present research were to design a stable, Ready to use (RTU) formulation of Rocuronium Bromide (RCB) Injection for Intravenous (IV) administration for storage at room temperature. Beta cyclodextrin (BCD) forms inclusion complexes with RCB. Edetate Disodium (EDTA) helps in achieving within the specification limit of Impurity C (Imp. C), a major metabolite of rocuronium bromide and Assay. Other excipients were selected to achieve a stable injectable formulation and cause less pain at the injection site. The formulation was optimized by Design of experiments (DoE) applying Central Composite Design (CCD) using Design Expert software and established design space where the formulation meets the desired acceptance criteria. The obtained optimized formulation can be terminally sterilized by moist heat and evaluated for thermal stability and robustness. The robustness of the formulation was established through Temperature excursion studies, pH sensitivity, and Oxygen sensitivity studies. Shelf life was estimated for 19 months when stored at 22°C which is an improvement to the currently available brands with 2-8°C storage. The formulation does not contain acetate buffer, which was identified as the root cause of the pain at the vascular site and may cause less vascular pain at the injection site. The current research work is encouraging in a positive way to achieve the objective of stable Rocuronium bromide injection at ambient conditions to enhance patient compliance.

A phase I randomized study to evaluate safety, pharmacokinetics, and pharmacodynamics of SIR2446M, a selective RIPK1 inhibitor, in healthy participants.

Activation of receptor-interacting protein kinase 1 (RIPK1), a broadly expressed serine/threonine protein kinase, by pro-inflammatory cytokines and pathogens can result in apoptosis, necroptosis, or inflammation. RIPK1 inhibition has been shown to reduce inflammation and cell damage in preclinical studies and may have therapeutic potential for degenerative and inflammatory diseases. SIR2446 is a potent and selective novel small molecule RIPK1 kinase inhibitor. This phase I, randomized, double-blind, placebo-controlled study in Australia (ACTRN12621001621808) evaluated the safety (primary objective), pharmacokinetics, and pharmacodynamics of single (3-600 mg) and multiple (5-400 mg for 10 days) ascending oral doses of SIR2446M (SIR2446 magnesium salt form) in healthy adults from Nov 24, 2021, until May 01, 2023. All treatment-emergent adverse events (TEAEs) were mild/moderate. The most reported TEAEs were vascular access site pain, headache, and rash morbilliform. SIR2446M plasma half-lives ranged from 11 to 19 h and there were no major deviations from dose proportionality for maximum concentration and area under the curve across doses. Renal excretion of unchanged SIR2446 was minimal. No marked accumulation was observed (mean accumulation ratio, 1.2-1.6) after multiple daily doses. A high-fat meal mildly reduced the exposure but was not considered clinically significant. SIR2446M had a rapid and sustained inhibitory effect on the activity of RIPK1, with an overall 90% target engagement at repeated doses ranging from 30 to 400 mg in peripheral blood mononuclear cells exvivo stimulated to undergo necroptosis. The favorable safety, pharmacokinetic, and pharmacodynamic profile of SIR2446M in healthy participants supports its further clinical development in patients with degenerative and inflammatory diseases.

Skill Proficiency, Efficacy, and Safety of the Transradial Approach in Transarterial Treatments for Hepatocellular Carcinoma.

Introduction Abdominal angiography procedures such as transarterial chemoembolization (TACE) are essential for hepatocellular carcinoma treatment. One method commonly used is transfemoral access (TFA). However, issues associated with this method, which include postoperative compression of the puncture site and long periods of bed rest, can affect patient satisfaction. Thus, transradial access (TRA), a minimally invasive treatment method that improves treatment quality, was developed for TACE. This retrospective, multicenter study aimed to investigate the efficacy and safety of abdominal angiography using the radial artery approach. Methods In total, 1,601 patients underwent abdominal angiography using TRA and received treatment (radial access for visceral intervention (RAVI)) at 14 institutions in Japan. The treatment time, procedure completion rate, patient satisfaction, and complications were investigated. Results The success rate of RAVI was 99.4%, and the complication rate was 1.2%. Approximately 98.2% of the patients requested the radial artery approach again. There were no significant differences in the success rate of RAVI and the incidence of complications based on the operator's years of experience or the patient's age. Some patients developed minor complications such as puncture site bleeding, hematoma, vascular pain, and vasospasm. Further, serious complications (cerebral infarction (n = 1), cerebellar infarction (n = 1), and aortic dissection (n = 1)) were observed. Conclusion Similar to the conventional TFA, RAVI helped in facilitating peritoneal angiography safely. In abdominal angiography, this method can reduce patient burden and can be widely used in the future from the perspective of clinical benefit.

Plant-Produced Therapeutic Crizanlizumab Monoclonal Antibody Binds P-Selectin to Alleviate Vaso-occlusive Pain Crises in Sickle Cell Disease.

Sickle Cell Disease (SCD) is a severe genetic disorder causing vascular occlusion and pain by upregulating the adhesion molecule P-selectin on endothelial cells and platelets. It primarily affects infants and children, causing chronic pain, circulatory problems, organ damage, and complications. Thus, effective treatment and management are crucial to reduce SCD-related risks. Anti-P-selectin antibody Crizanlizumab (Crimab) has been used to treat SCD. In this study, the heavy and light chain (HC and LC) genes of anti-P-Selectin antibody Crimab were cloned into a plant expression binary vector. The HC gene was under control of the duplicated 35S promoter and nopaline synthase (NOS) terminator, whereas the LC gene was under control of the potato proteinase inhibitor II (PIN2) promoter and PIN2 terminator. Agrobacterium tumefaciens LBA4404 was used to transfer the genes into the tobacco (Nicotiana tabacum cv. Xanthi) plant. In plants the genomic PCR and western blot confirmed gene presence and expression of HC and LC Crimab proteins in the plant, respectively. Crimab was successfully purified from transgenic plant leaf using protein A affinity chromatography. In ELISA, plant-derived Crimab (CrimabP) had similar binding activity to P-selectin compared to mammalian-derived Crimab (CrimabM). In surface plasmon resonance, the KD (dissociation binding constant) and response unit values were lower and higher than CrimabP, respectively. Taken together, these results demonstrate that the transgenic plant can be applied to produce biofunctional therapeutic monoclonal antibody.

The Effect of Cold Sand Pack on Percutaneous Coronary Intervention-Induced Vascular Complications and Pain: A Randomized Controlled Trial.

The aim of this study was to evaluate the effect of cold sand pack on vascular complications and pain in patients who undergoing percutaneous coronary intervention. This randomized controlled interventional trial was conducted in a hospital between November 30, 2021 and April 3, 2022. The patients were randomly assigned to CSP and NSP. A 5 kg sand pack was applied on the femoral area of the patients in the CSP group at an average temperature of 18.9°C for the first 20 minutes. A 5 kg sand pack was applied at an average temperature of 24.1°C after the procedure on the femoral region of the patients in the NSP group. After percutaneous coronary intervention, less bleeding developed in the CSP group at hours 2, 3, and 12 when compared to the NSP group, and the ecchymosis diameters measured at hours 1, 2, 3, 4, 5, 6, 12, and 24 were higher than those of the NSP patients (p < 0.05). It was detected that the pain score of the NSP group was higher at hours 1, 2, 3, 4, 5, 6, 12, and 24 on the femoral region when compared to the CSP group. It was detected that the cold sand pack applied for the first 20 minutes prevented bleeding and reduced ecchymosis diameter and pain intensity.

Potential Pathways and Pathophysiological Implications of Viral Infection-Driven Activation of Kallikrein-Kinin System (KKS).

Microcirculatory and coagulation disturbances commonly occur as pathological manifestations of systemic viral infections. Research exploring the role of the kallikrein-kinin system (KKS) in flavivirus infections has recently linked microvascular dysfunctions to bradykinin (BK)-induced signaling of B2R, a G protein-coupled receptor (GPCR) constitutively expressed by endothelial cells. The relevance of KKS activation as an innate response to viral infections has gained increasing attention, particularly after the reports regarding thrombogenic events during COVID-19. BK receptor (B2R and B1R) signal transduction results in vascular permeability, edema formation, angiogenesis, and pain. Recent findings unveiling the role of KKS in viral pathogenesis include evidence of increased activation of KKS with elevated levels of BK and its metabolites in both intravascular and tissue milieu, as well as reports demonstrating that virus replication stimulates BKR expression. In this review, we will discuss the mechanisms triggered by virus replication and by virus-induced inflammatory responses that may stimulate KKS. We also explore how KKS activation and BK signaling may impact virus pathogenesis and further discuss the potential therapeutic application of BKR antagonists in the treatment of hemorrhagic and respiratory diseases.

Analysis of Polyphenol Extract from Hazel Leaf and Ameliorative Efficacy and Mechanism against Hyperuricemia Zebrafish Model via Network Pharmacology and Molecular Docking.

Hazel leaf, a by-product of hazelnuts, is commonly used in traditional folk medicine in Portugal, Sweden, Iran and other regions for properties such as vascular protection, anti-bleeding, anti-edema, anti-infection, and pain relief. Based on our previous studies, the polyphenol extract from hazel leaf was identified and quantified via HPLC fingerprint. The contents of nine compounds including kaempferol, chlorogenic acid, myricetin, caffeic acid, p-coumaric acid, resveratrol, luteolin, gallic acid and ellagic acid in hazel leaf polyphenol extract (ZP) were preliminary calculated, among which kaempferol was the highest with 221.99 mg/g, followed by chlorogenic acid with 8.23 mg/g. The inhibition of ZP on α-glucosidase and xanthine oxidase activities was determined via the chemical method, and the inhibition on xanthine oxidase was better. Then, the effect of ZP on hyperuricemia zebrafish was investigated. It was found that ZP obviously reduced the levels of uric acid, xanthine oxidase, urea nitrogen and creatinine, and up-regulated the expression ofOAT1 and HPRT genes in hyperuricemia zebrafish. Finally, the targeted network pharmacological analysis and molecular docking of nine polyphenol compounds were performed to search for relevant mechanisms for alleviating hyperuricemia. These results will provide a valuable basis for the development and application of hazel leaf polyphenols as functional ingredients.

Comparing Injection Site Reactions of Aprepitant and Fosaprepitant in Gynecologic Cancer Chemotherapy.

The frequency rate of injection site reactions (ISR) due to fosaprepitant meglumine (Fos APR) has been shown to vary depending on the types of combined anticancer drug. This study aimed to elucidate the impact of Fos APR on ISR in patients receiving paclitaxel and carboplatin, with and without bevacizumab therapy (TC±Bev). This study focused on patients with gynecologic cancer (n=93) who received TC±Bev administration at Fujita Health University Hospital from March 2016 to February 2020, and monitored up to six cycles. The patients were randomly assigned to the Fos APR group (n=47) and the Aprepitant (APR) group (n=46). Using Visual Infusion Phlebitis (VIP) scores, ISR was evaluated by comparing the VIP scores of all cycles using a linear mixed model. The risk factors that contribute to the occurrence of vascular pain throughout all cycles were also examined. The VIP scores of all cycles showed a near significant intergroup difference (p=0.071). Factors that affected the development of vascular pain included Fos APR and age (p=0.027 and 0.049, respectively). Regarding age, patients aged <65 years had a higher risk. Four patients underwent a switch from the originally assigned neurokinin-1 receptor antagonist; in all of these cases, Fos APR was changed to APR for vascular pain. Fos APR may increase the risk for ISR associated with TC±Bev therapy for gynecological cancer.

Review of strategies to prevent infections related to ultrasound-guided nerve blocks and vascular access

Ultrasound guidance has become ubiquitous in the clinical practice of regional anesthesia and vascular access. Because the ultrasound transducer and an acoustic coupling medium (e.g. ultrasound gel) are applied directly to the patient’s body, the contact of a non-sterile ultrasound transducer with the site of intervention during the breach of the skin integrity by the needle carries the risk of infection transmission. Surprisingly, however, recommendations on how to prevent ultrasound-related outbreaks are often conflicting. With the increasing use of ultrasound in interventional procedures, such as vascular access, regional anesthesia, and pain medicine, the development of clear guidelines on how to prevent infection from patient to patient is essential for patient and operator safety. This review aims to provide a current understanding of the mechanisms and prevalence of infection transmission and to summarize the current recommendations for infectious precautions with interventional ultrasound. We also provide practically implementable and pragmatic recommendations for infectious precautions, based on the available information.

Analysis and Mechanism(s) of Hemophilia a Pain in Factor VIII Knockout Mice

Hemophilia A (HA) is characterized by spontaneous bleeding and pain. To understand mechanisms underlying HA pain, we developed models of chronic &amp; acute pain in FVIII knock-out (F8KO; B6;129S-F8tm1Kaz/J) male mice using innovative translatable measures to assess pain-related behaviors &amp; gait. We tested for: [i] mechanical hyperalgesia using von-Frey monofilaments; [ii] physical activity using weight-bearing with incapacitance meter and video recordings of free moving mice for locomotion (walking/running), grooming (licking/rubbing body) &amp; rearing (standing); and [iii] gait analysis during normal walking using in-house assembled MouseWalker with high-speed camera &amp; artificial intelligence (AI)-based algorithms. We observed significant increase in behavioral features of pain starting at ~8wks which continues to 20wks in F8KO Vs age matched B6 (p&amp;lt;0.05), including mechanical hyperalgesia, weight-bearing asymmetry, less time in locomotion, rearing &amp; grooming. Gait analysis of ~10wks F8KO showed lowered all-stance, increased body instability, single-swing &amp; posterior extreme position indices to compensate for body instability. This suggests that joint pain may interfere with weight-bearing &amp; locomotion in F8KO, consistent with joint pain, and affect daily activities such as walking in HA patients. To simulate bleeding-induced “ acute” pain, we gently inserted 30 G needle into sub patellar position of right hind leg of ~6wks old, anesthetized mice. F8KO showed significantly (p&amp;lt;0.05) reduced locomotion, rearing, grooming, %weight applied and increased mechanical sensitivity on injured limb at 4 days post-injury (4D PI) Vs uninjured (UI) F8KO lasting to 4wks PI for most of behavioral parameters suggesting that nociceptive inputs are induced at injury and pain persists after healing. We observed significant spatiotemporal gait alterations in F8KO PI Vs UI (p&amp;lt;0.05 for all features), including reduced stance duration, step length, swing speed and increased swing duration in the injured right hind limb (IRHL) indicative of avoidance of weight bearing on IRHL. To compensate, UI left hind limb (LHL) showed increased stance &amp; reduced swing duration on LHL &amp; left front limb (LFL). These data suggest that F8KO tends to spend shorter ground time on IRHL and longer airtime, compensated by UI LHL &amp; LFL. These observations are complementary to those of mice with sciatic nerve injury &amp; arthritis and patients with rheumatoid arthritis, ankylosing spondylitis, and gout. We observed significant (&amp;lt;0.05) alterations in interlimb coordination with decreased diagonal swing &amp; compensation with increased bound swing, the simultaneous motion of both FLs. A significant increase in all stance index could be compared to increased double support phase &amp; stance phase in patients with HA. F8KO 4D PI showed significant (p&amp;lt;0.05) increase in plasma serum amyloid P &amp; IL6 Vs UI F8KO &amp; injured B6 (IB6). Knee joint at 4D PI Vs UI F8KO &amp; IB6, showed expansion of synovial membrane with increased cellular infiltrate &amp; significant (p&amp;lt;0.05) increase in myeloperoxidase, neutrophil elastase +ve cells, degranulating mast cells, calcitonin gene related peptide (CGRP) and substance P (SP). H&amp;E and iron-stained sections of the knee joint ~8wks PI showed significant signs of hemarthropathy (p&amp;lt;0.05) Vs UI F8KO &amp; I B6. Interestingly, at ~14wks UI knee joint of F8KO showed significant stromal changes Vs UI B6 demonstrated by increased vasculature, iron stores &amp; mild synovial hyperplasia, indicative of subclinical bleeding that could trigger the transition to chronic pain with age. The underlying mechanisms involve inflammation, mast cell and neutrophil activation, and vascular changes, perhaps triggered by bleeding. Mast cell tryptase &amp; neutrophil elastase activate protease-activated receptor 2, which may cause nociceptor and endothelial activation, leading to vascular dysfunction and pain. SP and CGRP stimulate vascular permeability and arteriolar dilatation, respectively, and are involved in the generation and maintenance of pain. Thus, neuro-immune and neuro-vascular mechanisms underlie HA pain and may interfere with healing. We show features of pain, gait &amp; weight bearing changes in F8KO mice similar to those of HA patients. Sensory and gait tests used by us have the potential to develop objective measures of pain in HA. Gait changes in F8KO mice precede joint arthropathy, thus may be an early assessment tool in patients with HA.

Relationship of PIEZO1 and PIEZO2 vascular expression with diabetic neuropathy.

Introduction: Diabetic distal symmetric polyneuropathy (DDSP) is the most prevalent form of diabetic peripheral neuropathy, and 25% of patients develop pain in their toes. DDSP is associated with increased cutaneous microvessel density (MVD), reduced skin blood flow, endothelial dysfunction, and impaired fluid filtration with vasodilation. The Piezo family of mechanosensitive channels is known to be involved in the control of vascular caliber by converting mechanical force into intracellular signals. Furthermore, Piezo2 is particularly involved in peripheral pain mechanisms of DDSP patients. To date, very little is known about the number, structure, and PIEZO expression in cutaneous blood vessels (BVs) of individuals with DDSP and their relation with pain and time span of diabetes. Methods and results: We studied microvessels using endothelial markers (CD34 and CD31) and smooth cell marker (α-SMA) by indirect immunohistochemical assay in sections of the glabrous skin of the toes from patients and controls. MVD was assessed through CD34 and CD31 immunoreaction. MVD determined by CD34 is higher in short-term DDSP patients (less than 15 years of evolution), regardless of pain. However, long-term DDSP patients only had increased BV density in the painful group for CD31. BVs of patients with DDSP showed structural disorganization and loss of shape. The BVs affected by painful DDSP underwent the most dramatic structural changes, showing rupture, leakage, and abundance of material that occluded the BV lumen. Moreover, BVs of DDSP patients displayed a Piezo1 slight immunoreaction, whereas painful DDSP patients showed an increase in Piezo2 immunoreaction. Discussion: These results suggest that alterations in the number, structure, and immunohistochemical profile of specific BVs can explain the vascular impairment associated with painful DDSP, as well as the temporal span of diabetes. Finally, this study points out a possible correlation between increased vascular Piezo2 immunostaining and pain and decreased vascular Piezo1 immunostaining and the development of vasodilation deficiency.

Apply Anticoagulants after Discharge not Benefit to the Incidence of Symptomatic Thrombus in High-Altitude Areas: A Retrospective Study.

Many guidelines indicate that continuous use of anticoagulant drugs reduces the incidence of venous thrombus (VT), but no studies show the effect on the incidence of symptomatic venous thrombus (SVT) in total knee arthroplasty (TKA) patients after discharge. This study aimed to investigate whether it is necessary to apply anticoagulants to TKA patients after discharge. Patients who met the exclusion criteria requirement, underwent TKA by the same surgical team and received anticoagulant therapy after the operation were eligible for the study. Finally, a total of 567 TKA patients were recruited as participants. The patients were divided into two groups. The patients in group A were taken low molecular heparin for 5-10 days after surgery, which included but was not limited to low molecular weight heparin calcium injection (0.4 mL, ih, Qd), calcium dioxin injection (0.6 mL, ih, Qd), or enoxaparin sodium injection (0.4 mL, ih, Qd), and the patients needed to continue oral anticoagulant drug (10 mg, po, Qd) for 7-21 days after discharge. The patients in group B only took low molecular heparin 5-10 days after surgery and no treatment after discharge. The baseline characteristics of patients, total complications of SVT include lower limb vascular pain (LLVP), lower limb vascular pain no fester (LLVPNF), lower limbs swelling (LLS), lower limb fester (LLF), and death by thrombosis (DT), bleeding and mortality following discharged were compared between two groups. The study showed that the incidence of SVT patients had no significant difference between the two groups (p = 0.489). Moreover, the incidence of LLVP (p = 0.265), LLS (p = 0.84), LLVPNF (p = 0.213), LLF (p = 0.907), DT (p = 0.907), death from other causes, and bleeding (p = 0.323) had no significant differences between the two groups. However, the incidence of SVT in patients with smoking (p = 0.0001 or 0.0011) or drinking (p = 0.0002 or 0.0001) was significantly increased. There is not enough evidence showing that the TKA patients given anticoagulants after discharge had benefits in decreasing the risk of SVT. Furthermore, smoking and drinking would significantly increase the risk of SVT in TKA patients.

The Effect of Cold Application to the Lateral Neck Area on Peripheral Vascular Access Pain: A Randomised Controlled Study.

Various types of vagus nerve stimulation are employed in the treatment of a range of conditions, including depression, anxiety, epilepsy, headache, tinnitus, atrial fibrillation, schizophrenia, and musculoskeletal pain. The objective of this study was to apply vagal stimulation to the neck area using standardised cold, and then analyse the level of vascular access discomfort experienced by individuals who underwent venous cannulation from the dorsal side of the hand prior to anaesthesia. A total of 180 patients, aged 18-75, who were scheduled to undergo elective surgery, were categorised into three distinct groups: the Sham group (Group S), the Control group (Group K), and the Cold group (Group M), with each group consisting of 60 individuals. Bilateral cold application to the lateral side of the neck was performed prior to the commencement of vascular access in Group M patients, followed by the subsequent opening of vascular access. The alterations in heart rate among patients was assessed subsequent to the application of cold and following the establishment of vascular access. The participants were instructed to assess their level of vascular access pain on a numerical pain scale (NRS) ranging from 0 to 10. A statistically significant difference (p = 0.035) was seen when comparing the pain ratings of patients during vascular access. The study revealed that the NRS values exhibited a statistically significant decrease in Group M compared to both Group K (p = 0.038) and Group S (p = 0.048). Group M had a higher prevalence of individuals experiencing mild pain compared to other groups, and the difference was statistically significant (p = 0.029). In Group M, the average heart rate following vagal stimulation exhibited a statistically significant decrease compared to the average heart rate observed at the beginning of the study (p < 0.05). Upon comparing the original heart rate measurements with the heart rate values following vascular access, it was observed that there was an elevation in heart rate for both Group S and Group K. Conversely, Group M exhibited a decrease in heart rate after vascular access when compared to the initial heart rate values. In the present investigation, it was discovered that the application of cold to the neck region resulted in a drop in heart rate among the patients, which persisted throughout the process of vascular access. Furthermore, the level of pain experienced by these individuals was reduced during vascular access procedures.

350 Evaluation of analgesia prescribing in hospitalised adults ≥ 65

Abstract Background Pain is common in hospitalised patients aged ≥65. It is recommended to follow the World Health Organisation pain ladder but special consideration should be given to the adverse effects of opiates and Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). Methods A retrospective review of geriatric medicine inpatients aged ≥65 years was conducted. Data was collected from August 2023 over a 24-hour period using electronic patient records. Results One hundred and nineteen patient records were reviewed. The average age was 84 years (SD = 3.53 years); 56% female. One hundred and eleven patients (93%) were prescribed analgesia. Seventy patients (56%) had pain documented as a clinical issue with musculoskeletal (MSK) pain, the most common type at 64%(n = 45)), 10% (n = 7) undocumented pain source, 8.5%(n = 6) visceral pain, 8.5% (n = 6) vascular pain, 3% (n = 2) neuropathic pain, 3% (n = 2) cancer related pain, and 3% (n = 2) dental pain. Fifty-five patients (49.5%) were prescribed regular paracetamol, and fifty-one (46%) as required (PRN) paracetamol. Twenty-two (20%) were on a regular opiate and forty-two (38%) on a PRN opiate. Oramorph was the most common opiate prescribed (n = 26). Nineteen patients (17%) were on a regular NSAID; with twenty-one (19%) on a PRN NSAID. Topical diclofenac was the most common agent (28 patients). Sixteen (14%) patients were on a neuropathic agent, of which pregabalin was the most common (9 patients). 53% (N = 63) of patients were newly prescribed paracetamol, 26% (N = 31) opiates, 18% (N = 21) NSAIDs and 8% (N = 9) neuropathic agents. Twelve patients without an active pain issue were charted regular paracetamol. Thirty-four patients prescribed opiates had renal impairment. Conclusion There was a high rate of analgesia prescribing among older hospitalised patients (93%). Paracetamol was followed by opiates, NSAIDS and neuropathic agents in frequency. Issues identified include paracetamol over prescribing, NSAID underuse and use of opiates in renal impairment. These findings suggest that clinicians would benefit from a local guideline for the management of pain in the older population.

Diagnostic accuracy study of the clinical indicators of vascular trauma in patients undergoing antineoplastic chemotherapy in peripheral veins

Antineoplastic chemotherapy patients are susceptible to vascular trauma. The identification of this problem is possible through accurate clinical indicators. However, there are few diagnostic accuracy studies of vascular trauma in these patients. Thus, the objective was to analyze the accuracy of clinical indicators of vascular trauma in antineoplastic chemotherapy patients. A diagnostic accuracy study was carried out with a sample of 200 patients undergoing antineoplastic chemotherapy, in an oncology reference clinic, during 2018. A data collection form was created with sociodemographic and clinical data and indicators of vascular trauma. The sensitivity and specificity of the clinical indicators were assessed using a latent class analysis of random effects. The clinical indicators of decreased vascular elasticity (0.8384), pain (0.9573), and signs of infection at the catheter insertion site (0.9999) were specific for identifying vascular trauma in antineoplastic chemotherapy patients. The prevalence of vascular trauma in these patients was 11.17%. A set of three clinical indicators was considered accurate and statistically significant for confirming vascular trauma. This study has provided accurate clinical indicators of vascular trauma in antineoplastic chemotherapy patients. These results can contribute to establishing interventions, thereby reducing costs and maximizing health outcomes in this population.

1000-P: The Economic Impact of Reducing Hospitalizations and Amputations in Patients with Diabetic Foot Ulcers

The purpose of this real-word evidence (RWE) cohort study was to evaluate whether utilization of Cyclical Pressurized Topical Oxygen (TWO2) therapy had any impact on the incidence of Diabetic Foot Ulcer related hospitalizations and amputations over a 12-month period in patients with hard to heal Diabetic foot Ulcers (DFU). An IRB approved retrospective review of deidentified DFU patient medical records was conducted at 2 US Veterans Affairs Medical Centers in Illinois and Virginia, which included demographic information on wound characteristics, clinical characteristics, neuropathy, cardiovascular disease (CVD), peripheral vascular disease (PVD), pain levels and kidney disease etc. Within the unmatched cohorts of the 202 DFU patients (91 TWO2, 111 NO TWO2)there was an 88% reduction in hospitalizations and a 71% reduction in amputations over a 12-month period for the patients treated with TWO2 therapy compared to those that did not receive TWO2 therapy. Propensity score matching was conducted showing similar outcomes and a regression analysis as preformed along with a budget impact model which demonstrated significant cost saving to the payor system. This large RWE study demonstrates the TWO2 therapy positively impacts patients quality of life and the costs associated with treating their DFU by forcing them into remission, resulting in significantly reduced rates of hospitalizations, amputations and cost outlay. Disclosure M.G.Garoufalis: Consultant; Uluru, Employee; AOT Inc., Speaker's Bureau; 3M/KCI, Horizon Therapeutics plc.

ID: 208268 Treatment of Thalamic Stroke Pain With Spinal Cord Stimulation

Post-stroke pain occurs in patients who have sustained cerebrovascular lesions of the central somatosensory nervous system and occurs in up 10% of patients.1 The pain will emerge months or even years after initial injury. Symptoms are characterized as persistent neuropathic pain with allodynia and hyperesthesia. Patient often will develop complex regional pain syndrome due to this syndrome. Treatment options include anti-convulsants, anti-depressants, deep brain stimulation, repetitive transcranial magnetic stimulation, electrical motor cortex stimulation and spinal cord stimulation (SCS).2 SCS has been an effective in treatment of failed back surgery syndrome, complex regional pain syndrome, peripheral neuropathic pain and peripheral vascular disease pain.2 To our knowledge, this is the first case to demonstrate successful pain relief in a patient with hemi-body post- thalamic stroke pain syndrome using SCS at the cervical and thoracic level spine levels.

Microstructural Alteration of Trigeminal Nerve in Patients with Classic Trigeminal Neuralgia Shown by Diffusion Tensor Imaging and Its Correlation with Vascular Compression and Pain

To investigate the value of MR diffusion tensor imaging (DTI) in evaluating the microstructural alteration of trigeminal nerve in patients with classical trigeminal neuralgia (CTN) and its correlation with the degree of vascular compression and patient pain. A total of 108 patients with CTN were enrolled in this study. Patients were divided into 2 groups according to whether the asymptomatic side trigeminal nerve had neurovascular compression (NVC) or not: group A（32 cases）with NVC and group B（76 cases）without NVC. The anisotropy fraction (FA) and apparent diffusion coefficient (ADC) of bilateral trigeminal nerves were measured. Visual analogue scale (VAS) was used to evaluate the pain degree of the patients. The severity of NVC on the symptomatic side was classified as grade I, II and III by neurosurgeons according to the findings during microvascular decompression (MVD). The FA values of the trigeminal nerve on the symptomatic side were significantly lower than that on the asymptomatic side in group A ( P < 0.001) and group B (P < 0.001). 36 patients were treated with MVD, the FA values of the trigeminal nerve were grade I: 0.309 ± 0.011, grade II: 0.295 ± 0.015, grade III: 0.286±0.022, respectively, the difference was statistically significant ( P=0.011). The FA of the trigeminal nerve on the symptomatic side was negatively correlated with the degree of NVC and pain ( P < 0.05). Patients with NVC had significant decreases in FA and its negatively correlated with NVC and VAS scores.

Effects of time of bed rest on vascular complications after cardiac catheterization in pediatric patients with congenital heart disease: A randomized controlled trial

BackgroundPediatric cardiac catheterization, which is performed by accessing the femoral vessel, requires immobilization and bed rest for 4–6 h to prevent vascular complications. Studies in adults suggest that the immobilization time for the same access can be safely reduced to approximately 2 h after catheterization. However, it is unclear whether bed-rest time can be safely decreased after catheterization in children. ObjectiveTo assess the effects of bed-rest duration on bleeding, vascular complications, pain level, and the use of additional sedatives after transfemoral cardiac catheterization in children with congenital heart disease. MethodsThis study was an open-label, randomized, controlled, posttest-only design, including 86 children who underwent cardiac catheterization. Children were allocated to receive either 2 h of bed rest (n = 42) in the experimental group or 4 h of bed rest (n = 42) in the control group following catheterization. ResultsThe mean age of children was 3.93 (±3.82) years in the experimental group and 5.63 (±3.97) years in the control group. There was no difference in site bleeding incidence (P = 0.214), vascular complication score (P = 0.082), pain level (P = 0.445), or additional sedation use (P = 1.000) between the two groups. ConclusionsThere were no significant hemostatic complications after 2 h of bed rest following pediatric catheterization; therefore, 2 h of bed rest was as safe as 4 h of bed rest. (Trial registration: KCT0007737).