Role of polyunsaturated fatty acids in Japanese patients with coronary spastic angina.

BACKGROUND: n-3 polyunsaturated fatty acids (PUFAs) reduce the risk of ischemic heart disease. However, there are few reports of a relationship between n-3 PUFAs and coronary spastic angina (CSA). This study aimed to assess the age-dependent role of serum levels of fatty acid in patients with CSA. METHODS AND RESULTS: We enrolled 406 patients who underwent ergonovine tolerance test (ETT) during coronary angiography for evaluation of CSA. All ETT-positive subjects were diagnosed as having CSA. We categorized the patients by age and results of ETT as follows: (1) young (age ≤ 65 years) CSA-positive (n = 32), (2) young CSA-negative (n = 134), (3) elderly (age > 66 years) CSA-positive (n = 36), and (4) elderly CSA-negative (n = 204) groups. We evaluated the serum levels of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid, and dihomo-gamma-linolenic acid. In the young groups, the serum levels of EPA (64.3 ±â€¯37.7 µg/mL vs. 49.4 ±â€¯28.8 µg/mL, p = 0.015) and DHA (135.7 ±â€¯47.6 µg/mL vs. 117.4 ±â€¯37.6 µg/mL, p = 0.020) were significantly higher in the CSA-positive group than in the CSA-negative group, respectively. However, this was not the case with elderly groups. In the multivariate analysis in young groups, the serum levels of EPA (p = 0.028) and DHA (p = 0.049) were independently associated with the presence of CSA, respectively. CONCLUSION: Our results suggested that the higher serum levels of EPA and/or DHA might be involved in the pathophysiology of CSA in the young population but not in the elderly population.

Mephentermine dependence in a young Indian adult without psychosis.

Mephentermine is a vasopressor drug closely related to amphetamine and methamphetamine. Cases of abuse and dependence to mephentermine have dotted medical literature for a long time. Till date, 11 cases of dependence to mephentermine have been published. In this report, a case of mephentermine dependence is being discussed. The patient was a young adult male who was dependent to mephentermine for nearly 3 years. He was an athlete and was introduced to mephentermine by his peer for enhancing performance. He did not develop any major physical or psychiatric issue due to the drug. He was managed on out patient basis. Though cases of mephentermine dependence are few and far in medical literature, reports from other sources indicate that the problem could be more common and could be on rise. High index of suspicion and holistic care is likely to help patients and treating clinicians.

Increase in early wound leakage in total knee arthroplasty with local infiltrative analgesia (LIA) that includes epinephrine: a retrospective cohort study.

Background and purpose - After introducing a new local infiltration anesthesia (LIA) protocol with addition of 30 mL ropivacaine 2% and 1 mg epinephrine, we noted an increase in early wound leakage. As wound leakage is associated with prosthetic joint infection, our department aims to minimize postoperative wound leakage. This study evaluates the incidence of early wound leakage and postoperative pain after knee arthroplasty (KA) following adjustment of the LIA protocol with addition of 30 cc ropivacaine 2% and 1 mg epinephrine. Patients and methods - In this retrospective medical dossier study all patients (n = 502) undergoing a primary total or unicondylar knee arthroplasty between January 1, 2018 and July 1, 2019 were included. Patients received an LIA protocol containing 120 mL 2 mg/mL ropivacaine (ROPI- group; n = 256). After October 30, patients received an LIA protocol containing 150 mL 2 mg/mL ropivacaine with 1 mg epinephrine in the first 100 mL (ROPI + group; n = 246). The primary outcome measure was early wound leakage (< 72 hours postoperatively), defined as wound fluid leaking past the barrier of the wound dressing. Secondary outcome measure, 10-point numeric rating scale (NRS) pain (< 72 hours postoperatively) was also assessed. Data was evaluated using logistic regression. Results - The incidence of wound leakage was higher in the ROPI + group: 24% versus 17% in the ROPI- group (p = 0.06). After adjusting for the differences between surgeons the relative risk of this increase was 1.4 (1.0-2.0). The ROPI + and ROPI- group were similar regarding postoperative pain assessment. Interpretation - Adjustment of the LIA protocol with 30 mL 2% ropivacaine and 1 mg epinephrine led to an increase in early wound leakage in knee arthroplasty but no difference in pain scores.

Wide-Awake Surgery With Local Anesthesia and Epinephrine Is Safe.

Hand and upper extremity surgery performed with the patient wide awake involves the use of a local anesthetic and epinephrine. Controversy persists as to whether epinephrine is safe for use in the hand. The goal of this study was to evaluate the safety of epinephrine in hand and upper extremity surgery. The hypothesis was that epinephrine is safe and can be used for a wide breadth of surgical procedures of the hand and upper extremity. A 4-year retrospective chart review was conducted of consecutive patients undergoing wide-awake surgery performed by 2 surgeons at a single institution. All procedures were performed with local anesthesia and epinephrine. Data collected included patient demographics, procedure volume, procedure type, surgical setting, and complications related to epinephrine use. During the study period, 4054 consecutive patients underwent 4287 wide-awake procedures with local anesthesia and epinephrine. Average patient age was 59 years, and 64% of patients were female. No complications occurred as a result of the use of epinephrine, and no tissue necrosis, phentolamine reversal, anaphylaxis, or readmissions occurred. No patients required conversion to general anesthesia or monitored anesthesia care. This analysis of more than 4000 consecutive patients undergoing wide-awake hand and upper extremity surgery with epinephrine confirmed that epinephrine use is safe, with no reported cases of tissue necrosis, reversal, readmission, anaphylaxis, or anesthetic conversion. Epinephrine is safe for use in the hand and upper extremity for patients undergoing wide-awake hand surgery with a local anesthetic. [Orthopedics. 2020;43(6):e529-e532.].

Keeping the Finger on the Pulse: Cardiac Arrhythmias in Hand Surgery Using Local Anesthesia with Adrenaline.

BACKGROUND: The wide-awake local anesthesia no tourniquet (WALANT) technique in hand surgery is gaining popularity. The authors aimed to prospectively analyze the frequency and type of arrhythmias in patients undergoing hand surgery under local anesthesia and to examine whether the addition of adrenaline affects their incidence. METHODS: Adult patients undergoing hand surgery under local anesthesia were randomized into two groups: group 1, local anesthesia with lidocaine and tourniquet; and group 2, local anesthesia with lidocaine and adrenaline (WALANT). Patients with a history of arrhythmias were excluded. Patients were connected to Holter electrocardiographic monitoring before surgery and up until discharge. The records were blindly compared between the groups regarding types of arrhythmias, and frequency and timing relative to injection and tourniquet inflation. RESULTS: One hundred two patients were included between August of 2018 and August of 2019 (age, 59.7 ± 13.6 years; 71 percent women; 51 in each group). No major arrhythmia (ventricular tachycardia, ventricular fibrillation, atrial fibrillation) or arrhythmia-related symptoms were recorded for either group. Minor arrhythmias (including atrial premature beats, ventricular premature beats, and atrial tachycardia) were recorded in 68 patients (66.6 percent), with no statistical difference between the groups. There were three patients with minor arrhythmias during inflation of the tourniquet. Patients in the adrenaline group had 2 percent sinus tachycardia during injection and 4 percent asymptomatic bradyarrhythmias. These findings do not require any further treatment. CONCLUSIONS: The authors' results show that hand operations using WALANT technique in patients with no history of arrhythmia are safe and are not arrhythmogenic; therefore, there is no need for routine perioperative continuous electrocardiographic monitoring. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

The Headache Pipeline: Excitement and Uncertainty.

There are many new treatment options available for migraine and more are coming. Three calcitonin gene-related peptide (CGRP) antagonist monoclonal antibodies have been approved and a 4th is due in early 2020. Small molecule CGRP receptor-blocking oral compounds, both for acute care and prevention, are also coming. Four neurostimulators are available, with others on the way. New acute treatments coming soon include the 5HT1F agonist lasmiditan, a zolmitriptan intradermal micro-needle patch, and a nasal mist sumatriptan with a permeability enhancer. Farther out, three novel dihydroergotamine delivery systems, and a liquid-filled capsule of celecoxib show early promise. A new, safer form of methysergide is in the works, as is a longer-duration onabotulinumtoxinA. As always with new products, questions regarding safety, tolerability, cost, and insurance coverage will need to be addressed. Despite these concerns and uncertainties, a robust headache treatment pipeline is good for patients who are not satisfied with the results of their treatment and/or cannot tolerate existing treatments.

Lessening Organ dysfunction with VITamin C (LOVIT): protocol for a randomized controlled trial.

BACKGROUND: Sepsis is a health problem of global importance; treatments focus on controlling infection and supporting failing organs. Recent clinical research suggests that intravenous vitamin C may decrease mortality in sepsis. We have designed a randomized controlled trial (RCT) to ascertain the effect of vitamin C on the composite endpoint of death or persistent organ dysfunction at 28 days in patients with sepsis. METHODS: LOVIT (Lessening Organ dysfunction with VITamin C) is a multicenter, parallel-group, blinded (participants, clinicians, study personnel, Steering Committee members, data analysts), superiority RCT (minimum n = 800). Eligible patients have sepsis as the diagnosis for admission to the intensive care unit (ICU) and are receiving vasopressors. Those admitted to the ICU for more than 24 h are excluded. Eligible patients are randomized to high-dose intravenous vitamin C (50 mg/kg every 6 h for 96 h) or placebo. The primary outcome is a composite of death or persistent organ dysfunction (need for vasopressors, invasive mechanical ventilation, or new and persisting renal replacement therapy) at day 28. Secondary outcomes include persistent organ dysfunction-free days to day 28, mortality and health-related quality of life at 6 months, biomarkers of dysoxia, inflammation, infection, endothelial function, and adverse effects (hemolysis, acute kidney injury, and hypoglycemia). Six subgroup analyses are planned. DISCUSSION: This RCT will provide evidence of the effect of high-dose intravenous vitamin C on patient-important outcomes in patients with sepsis. TRIAL REGISTRATION: clinicaltrials.gov, NCT03680274, first posted 21 September 2018.

Onset Time of Local Anesthesia After Single Injection in Toe Nerve Blocks: A Randomized Double-Blind Trial.

PURPOSE: The study was conducted to investigate the onset time and safety profile of four different local anesthetic solutions. DESIGN: Randomized controlled clinical trial study. METHODS: One hundred twelve healthy volunteers were assigned to receive digital block on their second toe. Individuals were randomly assigned to one of the following groups: lidocaine 2%, lidocaine 2% with epinephrine, bupivacaine 0.5%, or bupivacaine 0.5% with epinephrine. Onset time was measured until detecting the absence of pinprick sensation. Oxygen saturation was measured in the infiltrated toe up to 60 minutes. FINDINGS: The subjects in the groups of anesthetics with epinephrine had a significantly lower mean onset time. There were no significant differences regarding oxygen saturation between the groups and no adverse effects were recorded. CONCLUSIONS: The use of anesthetics with epinephrine can be an effective form of local anesthetic for digital blocks when a rapid onset of action, prolonged duration of anesthesia, and vasoconstrictive action are required.

Acute Ischemia of the Glans Penis after Circumcision Treated with Hyperbaric Therapy and Pentoxifylline: Case Report and Revision of the Literature.

Acute severe ischemia of glans penis after circumcision is a very rare event and, if not treated, can lead to irreversible necrosis with severe consequences such as loss of part of the penis. The possible causes for this condition could be blood-vessel binding or cauterization, dorsal penile nerve block (DPNB), local anesthesia with vasoconstricting agents and wound dressing compression. The aim of the treatment is to provide good blood supply and thus, oxygen delivery to the ischemic penis. The therapeutic options include hyperbaric therapy (HBOT), pentoxifylline (PTX), enoxaparina, iloprost, antiplatelet, corticosteroids and peridural anesthesia. We report the case of a 24-year-old male who developed an acute severe glans penis ischemia after circumcision done under DPNB. The patient was successfully treated with HBOT in combination with PTX.

Local anaesthetics combined with vasoconstrictors in patients with cardiovascular disease undergoing dental procedures: systematic review and meta-analysis protocol.

INTRODUCTION: The use of vasoconstrictors combined with local anaesthetics (LAs) in dentistry for patients with cardiovascular disease (CVD) is still controversial in the scientific literature. It raises concerns regarding the possibility of transient episodes, triggering negative cardiovascular outcomes. METHOD/DESIGN: Trials eligible for our systematic review will enrol patients with CVD who have undergone dental treatments carried out with the use of LAs by comparing two arms: LAs with vasoconstrictors and LAs without vasoconstrictors. The research will be conducted in the electronic databases, namely Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Healthstar (via Ovid), Cumulative Index to Nursing and Allied Health Literature and Web of Science, from their inception to December 2017, without any restrictions in terms of language and status of publication. A team of reviewers will independently assess titles, abstracts and complete text to determine eligibility. For eligible studies, the same reviewers will perform data extraction and evaluate the risk of bias in the selected articles. The selected outcomes comprise death, mortality by a specific cause, stroke, acute myocardial infarction, hospitalisation, pain, bleeding, arrhythmias, ischaemic episodes, anxiety, adverse effects, changes in blood pressure, changes in heart rate, anxiety and results obtained via oximetry. Whenever possible, we will conduct a meta-analysis to establish the effects of LAs with and without vasoconstrictors in the patients with CVD, and the overall quality of evidence for each outcome will be determined using the Grading of Recommendations Assessment, Development and Evaluation classification system. ETHICS AND DISSEMINATION: Ethics committee approval was not necessary because this is a protocol of systematic review. This systematic review will be submitted for presentation at conferences and for publication in a peer-reviewed journal. Our review will assess the risks of cardiovascular events when using LAs with and without vasoconstrictors in patients with CVD, focusing on important clinical outcomes. PROSPERO REGISTRATION NUMBER: CRD42016045421.

Best clinical practice guidance for local analgesia in paediatric dentistry: an EAPD policy document.

BACKGROUND: The European Academy of Paediatric Dentistry (EAPD) proposes this best-practice guidance to help practitioners to decide when and how to use local analgesia to control pain in children, adolescents, and medically compromised individuals during the delivery of oral health care. METHODS: A search of different databases was conducted using all terms relevant to the subject. Relevant papers were identified after a review of their titles, abstracts or full papers. Three workshops were held during the corresponding EAPD interim seminar in Torino (Italy) in 2017. Several statements were agreed upon and, furthermore, knowledge gaps were identified. RESULTS: An important outcome was that when local analgesia administered appropriately-correct choice of agent(s) and dosage, proper route of administration-it is, firstly, clinically effective for pain-control in treating children and, secondly, it carries a very low risk of morbidity including adverse or side-effects. Furthermore, several gaps in knowledge were identified during the workshop which indicates future research needs. Most importantly it remains unsatisfactory that in several European countries the most frequently used injectable local analgesic agent, articaine, is not approved for usage in children below the age of 4 years. CONCLUSION: When considering the dental demand to treat vulnerable (medically compromised) children and adolescents in a safe, painless, less-invasive and effective way, there seems to be an urgent need to close these gaps in knowledge.

Wide Awake Hand Surgery.

Wide awake hand surgery employs local-only anesthesia with low-dose epinephrine to create a bloodless field without the use of an arm tourniquet. Despite traditional teaching, evidence-based medicine suggests epinephrine is safe for use in hand and digital anesthesia. Eliminating an arm tourniquet reduces the requirement for sedation and general anesthetic. This confers particular advantage in surgeries such as tendon repairs, tendon transfers, and soft tissue releases in which intraoperative active motion can used to optimize outcomes. The wide awake approach also confers significant benefit to patients, providers, and health care systems alike due to efficiencies and cost savings.

The Hydroalcoholic Extract of Leaves of Mandevilla moricandiana Induces NO-Mediated Vascular Relaxation.

Natural products extracted from plants represent a valuable source of new bioactive substances. Many studies describe the potential of plant products for the treatment of cardiovascular diseases. Species of the Mandevilla genus have been studied for their biological activities, mainly as antioxidant, anti-inflammatory, and vasorelaxant. However, the phytochemical and pharmacological profiles of Mandevilla moricandiana have not been investigated yet. The aim of this study was to evaluate the vasodilator effect of the hydroalcoholic extract of the leaves of M. moricandiana, as well as its chemical profile. Chemical analysis and quantification of major compounds were performed by HPLC analysis. Total flavonoid content was quantified based on rutin equivalents, and major compounds were identified based on HPLC-DAD-MS analysis. M. moricandiana leaf extract-induced vasodilation was investigated in rat aortic rings precontracted with phenylephrine. The total flavonoids were quantified as 3.25 ± 0.11 % w/w of the hydroalcoholic leaf extract, and HPLC-DAD-MS allowed for the identification of luteolin and quercetin glycosides. The maximal relaxant effect of the hydroalcoholic leaf extract was 86.07 ± 1.68 % at a concentration of 30 µg/mL (p < 0.05; n = 6). The concentration of hydroalcoholic extract of the leaves of M. moricandiana necessary to reduce phenylephrine-induced contractions of the endothelium-intact aorta by 50 % was 0.82 ± 0.10 µg/mL. M. moricandiana leaf extract-induced vasodilation was abolished in aortas pretreated with NG-nitro-L-arginine methyl ester and 1H-[1,2,4]oxadiazolo-[4,3-α]quinoxalin-1-one. In addition, diphenhydramine partially inhibited the effect of the hydroalcoholic extract of the leaves of M. moricandiana. Thus, M. moricandiana-induced relaxation depends on the endothelium and on the activation of the nitric oxide/cyclic GMP pathway, with the involvement of endothelial histamine H1 receptors. Luteolin and quercetin glycosides seem to contribute to the extract activity.

The Pathophysiology of Early Hypotension Following Epinephrine-containing Local Anesthetic Infiltration of the Nasal Mucosa in Patients Undergoing Endoscopic Transsphenoidal Hypophysectomy: A Prospective, Observational Study.

In patients undergoing endoscopic transsphenoidal hypophysectomy, the nasal mucosa is often infiltrated with local anesthetic solutions that contain epinephrine to aid hemostasis. This may, however, result in hemodynamic changes, especially hypotension. We characterized the cardiovascular changes using a LiDCOrapid monitor in 13 patients after the infiltration of 4% articaine containing 1:200,000 epinephrine. Nine (69%) had a >20% decrease in mean arterial pressure at a median time of 116 seconds after the infiltration of articaine with epinephrine. Analysis of the cardiac output data revealed that this was caused by a sustained reduction in systemic vascular resistance. The arterial blood pressure normalized over a period of 60 to 90 seconds secondary to increases in stroke volume and heart rate producing an elevation in cardiac output. Transient hypotension following the infiltration of epinephrine-containing local anesthetics may be caused by epinephrine stimulation of ß2-adrenoceptors producing vasodilation.

Critical neural targets for (the level of) human consciousness: Arousal arrest and unconsciousness after sumatriptan administration.

BACKGROUND: Insufficient understanding of the mechanisms of consciousness can make unconsciousness a diagnostic challenge, directly effecting the treatment and the outcome of the patient. Consciousness is a product of brainstem arousal (wakefulness, the level of consciousness) and cortical information integration (awareness, the contents of consciousness). The thalamus serves as a critical hub in the arousal pathway. The nuclei within the internal medullary lamina, together with the associated thalamocortical connections, have been implicated as being especially important for human consciousness. CASE STUDY: A 17-year old male migraineur developed a sudden episode of unconsciousness after receiving a single dose of intranasal sumatriptan for the treatment of prolonged migraine-associated symptoms. Diffusion-weighted magnetic resonance imaging revealed a small bilateral thalamic infarction affecting the centromedian and parafascicular nuclei and the associated non-specific thalamocortical connections as the likely reason for the impairment of consciousness. With the exception of occasional fatigue due to a persistent lesion on the left thalamus, the patient experienced full recovery. Corresponding to the injury, diffusion tensor tractography imaging revealed a distinctive defect on the thalamocortical fibres originating from the left centromedian/parafascicular nuclei complex. CONCLUSIONS: The presented case offers an outstanding example of the importance of the arousal system and non-specific thalamocortical connectivity for normal waking consciousness.

Posterior reversible encephalopathy syndrome with thalamic involvement during vasopressor treatment of vertebrobasilar vasospasm after subarachnoid hemorrhage.

Hemodynamic augmentation is the primary medical intervention employed to reverse neurological deficits associated with vasospasm and delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage. Failure to improve despite induced hypertension (IH) may raise concern for persistent hypoperfusion and prompt even more aggressive blood pressure augmentation. However, posterior reversible encephalopathy syndrome (PRES) is a hyperperfusion syndrome reported as a rare complication of IH that may confound this picture. We report a case of PRES with prominent thalamic involvement and impaired level of consciousness secondary to blood pressure augmentation for the treatment of symptomatic vertebrobasilar vasospasm. Recognition of this syndrome in distinction to worsening ischemia is particularly critical, as normalization of blood pressure should lead to rapid clinical improvement.

Posterior reversible encephalopathy syndrome with thalamic involvement during vasopressor treatment of vertebrobasilar vasospasm after subarachnoid hemorrhage.

Hemodynamic augmentation is the primary medical intervention employed to reverse neurological deficits associated with vasospasm and delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage. Failure to improve despite induced hypertension (IH) may raise concern for persistent hypoperfusion and prompt even more aggressive blood pressure augmentation. However, posterior reversible encephalopathy syndrome (PRES) is a hyperperfusion syndrome reported as a rare complication of IH that may confound this picture. We report a case of PRES with prominent thalamic involvement and impaired level of consciousness secondary to blood pressure augmentation for the treatment of symptomatic vertebrobasilar vasospasm. Recognition of this syndrome in distinction to worsening ischemia is particularly critical, as normalization of blood pressure should lead to rapid clinical improvement.