Showing papers on "Epinephrine published in 2017"

Epinephrine for First-aid Management of Anaphylaxis.

Abstract: Anaphylaxis is a severe, generalized allergic or hypersensitivity reaction that is rapid in onset and may cause death. Epinephrine (adrenaline) can be life-saving when administered as rapidly as possible once anaphylaxis is recognized. This clinical report from the American Academy of Pediatrics is an update of the 2007 clinical report on this topic. It provides information to help clinicians identify patients at risk of anaphylaxis and new information about epinephrine and epinephrine autoinjectors (EAs). The report also highlights the importance of patient and family education about the recognition and management of anaphylaxis in the community. Key points emphasized include the following: (1) validated clinical criteria are available to facilitate prompt diagnosis of anaphylaxis; (2) prompt intramuscular epinephrine injection in the mid-outer thigh reduces hospitalizations, morbidity, and mortality; (3) prescribing EAs facilitates timely epinephrine injection in community settings for patients with a history of anaphylaxis and, if specific circumstances warrant, for some high-risk patients who have not previously experienced anaphylaxis; (4) prescribing epinephrine for infants and young children weighing <15 kg, especially those who weigh 7.5 kg and under, currently presents a dilemma, because the lowest dose available in EAs, 0.15 mg, is a high dose for many infants and some young children; (5) effective management of anaphylaxis in the community requires a comprehensive approach involving children, families, preschools, schools, camps, and sports organizations; and (6) prevention of anaphylaxis recurrences involves confirmation of the trigger, discussion of specific allergen avoidance, allergen immunotherapy (eg, with stinging insect venom, if relevant), and a written, personalized anaphylaxis emergency action plan; and (7) the management of anaphylaxis also involves education of children and supervising adults about anaphylaxis recognition and first-aid treatment.

Inflammation and exercise: Inhibition of monocytic intracellular TNF production by acute exercise via β 2 -adrenergic activation

Abstract: Regular exercise is shown to exert anti-inflammatory effects, yet the effects of acute exercise on cellular inflammatory responses and its mechanisms remain unclear. We tested the hypothesis that sympathoadrenergic activation during a single bout of exercise has a suppressive effect on monocytic cytokine production mediated by β2 adrenergic receptors (AR). We investigated the effects of 20-min moderate (65-70% VO2 peak) exercise-induced catecholamine production on LPS-stimulated TNF production by monocytes in 47 healthy volunteers and determined AR subtypes involved. We also examined the effects of β-agonist isoproterenol and endogenous β- and α-agonists epinephrine and norepinephrine, and receptor-subtype-specific β- and α-antagonists on TNF production in a series of in vitro investigations. LPS-stimulated TNF production by peripheral blood monocytes was determined intracellularly by flow cytometry, using an intracellular protein transport inhibitor. Percent TNF-producing monocytes and per-cell TNF production with and without LPS was suppressed by exercise with moderate to large effects, which was reversed by a β2-AR antagonist in spite that plasma TNF levels did not change. This inhibitory response in TNF production by exercise was mirrored by β-AR agonists in an agonist-specific and dose-dependent manner in vitro: similar isoproterenol (EC50=2.1-4.7×10-10M) and epinephrine (EC50=4.4-10×10-10M) potency and higher norepinephrine concentrations (EC50=2.6-4.3×10-8M) needed for the effects. Importantly, epinephrine levels observed during acute exercise in vivo significantly inhibited TNF production in vitro. The inhibitory effect of the AR agonists was abolished by β2-, but not by β1- or α-AR blockers. We conclude that the downregulation of monocytic TNF production during acute exercise is mediated by elevated epinephrine levels through β2-ARs. Decreased inflammatory responses during acute exercise may protect against chronic conditions with low-grade inflammation.

Impact of school peanut-free policies on epinephrine administration

Abstract: Background Children with food allergies spend a large proportion of time in school but characteristics of allergic reactions in schools are not well studied. Some schools self-designate as peanut-free or have peanut-free areas, but the impact of policies on clinical outcomes has not been evaluated. Objective We sought to determine the effect of peanut-free policies on rates of epinephrine administration for allergic reactions in Massachusetts public schools. Methods In this retrospective study, we analyzed (1) rates of epinephrine administration in all Massachusetts public schools and (2) Massachusetts public school nurse survey reports of school peanut-free policies from 2006 to 2011 and whether schools self-designated as "peanut-free" based on policies. Rates of epinephrine administration were compared for schools with or without peanut-restrictive policies. Results The percentage of schools with peanut-restrictive policies did not change significantly in the study time frame. There was variability in policies used by schools self-designated as peanut-free. No policy was associated with complete absence of allergic reactions. Both self-designated peanut-free schools and schools banning peanuts from being served in school or brought from home reported allergic reactions to nuts. Policies restricting peanuts from home, served in schools, or having peanut-free classrooms did not affect epinephrine administration rates. Schools with peanut-free tables, compared to without, had lower rates of epinephrine administration (incidence rate per 10,000 students 0.2 and 0.6, respectively, P = .009). Conclusions These data provide a basis for evidence-based school policies for children with food allergies. Further studies are required before decisions can be made regarding peanut-free policies in schools.

Digital Necrosis After Lidocaine and Epinephrine Injection in the Flexor Tendon Sheath Without Phentolamine Rescue.

Abstract: The literature generally supports the safety of epinephrine injection in the digits, but recent case reports describe ischemic adverse events associated with the use of lidocaine and epinephrine in which phentolamine rescue was not performed. We present a case of finger necrosis and subsequent amputation in a patient after 1% lidocaine with 1:100,000 epinephrine was injected in the fat and flexor sheaths in the palm for a 3-finger trigger release. Phentolamine rescue was not performed. All surgeons who use epinephrine in the finger should be prepared to reverse vasoconstriction with phentolamine rescue if there is persistently inadequate perfusion of the fingertip.

Cardiovascular Manifestations of Pheochromocytoma.

Abstract: Pheochromocytomas are rare endocrine tumors that can have a significant impact on a variety of organ systems, including the cardiovascular system. Although the pathophysiology is not completely understood, pheochromocytomas exert their effects through high levels of catecholamines, mainly epinephrine and norepinephrine, which stimulate adrenergic receptors, including those within the cardiovascular system. Although the most common cardiovascular manifestation is hypertension, patients with pheochromocytoma can present with arrhythmia, hypotension, shock, myocardial ischemia, cardiomyopathy, aortic dissection, and peripheral ischemia. The medical management of the cardiovascular effects of pheochromocytoma is via blockade of adrenergic receptors, usually through the use of alpha blockers, with the addition of beta blockers if needed. However, only surgical resection of the pheochromocytoma is potentially curative, and this tumor requires unique management perioperatively. Because of the variability of presentation and the significant morbidity and mortality of patients with an undiagnosed pheochromocytoma, this entity should not be overlooked in the evaluation of patients with a wide variety of cardiovascular disorders.

How to manage anaphylaxis in primary care.

Abstract: Anaphylaxis is defined as a severe life-threatening generalized or systemic hypersensitivity reaction characterized by rapidly developing airway and/or circulation problems. It presents with very different combinations of symptoms and apparently mild signs and can progress to fatal anaphylactic shock unpredictably. The difficulty in recognizing anaphylaxis is due, in part, to the variability of diagnostic criteria, which in turn leads to a delay in administration of appropriate treatment, thus increasing the risk of death. The use of validated clinical criteria can facilitate the diagnosis of anaphylaxis. Intramuscular epinephrine (adrenaline) is the medication of choice for the emergency treatment of anaphylaxis. Administration of corticosteroids and H1-antihistamines should not delay the administration of epinephrine, and the management of a patient with anaphylaxis should not end with the acute episode. Long-term management of anaphylaxis should include avoidance of triggers, following confirmation by an allergology study. Etiologic factors suspected in the emergency department often differ from the real causes of anaphylaxis. Evaluation of patients with a history of anaphylaxis should also include an assessment of personal data, such as age and comorbidities, which may increase the risk of severe reactions. Special attention should also be paid to co-factors, as these may easily confound the cause of the anaphylaxis. Patients experiencing anaphylaxis should administer epinephrine as soon as possible. Education (including the use of Internet and social media), written personalized emergency action plans, and self-injectable epinephrine have proven useful for the treatment of further anaphylaxis episodes.

Stress Hormones Epinephrine and Corticosterone Selectively Modulate Herpes Simplex Virus 1 (HSV-1) and HSV-2 Productive Infections in Adult Sympathetic, but Not Sensory, Neurons.

Abstract: Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) infect and establish latency in peripheral neurons, from which they can reactivate to cause recurrent disease throughout the life of the host. Stress is associated with the exacerbation of clinical symptoms and the induction of recurrences in humans and animal models. The viruses preferentially replicate and establish latency in different subtypes of sensory neurons, as well as in neurons of the autonomic nervous system that are highly responsive to stress hormones. To determine if stress-related hormones modulate productive HSV-1 and HSV-2 infections within sensory and autonomic neurons, we analyzed viral DNA and the production of viral progeny after treatment of primary adult murine neuronal cultures with the stress hormones epinephrine and corticosterone. Both sensory trigeminal ganglion (TG) and sympathetic superior cervical ganglion (SCG) neurons expressed adrenergic receptors (activated by epinephrine) and the glucocorticoid receptor (activated by corticosterone). Productive HSV infection colocalized with these receptors in SCG but not in TG neurons. In productively infected neuronal cultures, epinephrine treatment significantly increased the levels of HSV-1 DNA replication and production of viral progeny in SCG neurons, but no significant differences were found in TG neurons. In contrast, corticosterone significantly decreased the levels of HSV-2 DNA replication and production of viral progeny in SCG neurons but not in TG neurons. Thus, the stress-related hormones epinephrine and corticosterone selectively modulate acute HSV-1 and HSV-2 infections in autonomic, but not sensory, neurons.IMPORTANCE Stress exacerbates acute disease symptoms resulting from HSV-1 and HSV-2 infections and is associated with the appearance of recurrent skin lesions in millions of people. Although stress hormones are thought to impact HSV-1 and HSV-2 through immune system suppression, sensory and autonomic neurons that become infected by HSV-1 and HSV-2 express stress hormone receptors and are responsive to hormone fluctuations. Our results show that autonomic neurons are more responsive to epinephrine and corticosterone than are sensory neurons, demonstrating that the autonomic nervous system plays a substantial role in HSV pathogenesis. Furthermore, these results suggest that stress responses have the potential to differentially impact HSV-1 and HSV-2 so as to produce divergent outcomes of infection.

of Subcutaneously Administered Epinephrine and Terbutaline in Patients with Reversible Airway Obstruction

Abstract: The cardiopulmonary effects of epinephrine and terbutaline were compared in a doubleblind crossover study in 23 subjects with chronic obstructive airway disease. On each of three days each subject received a single subcutaneous dose of saline, 0.25 mg of epinephrine or 0.5 mg of terbutaline. Treatment with epinephrine produced significant increases in forced vital capacity (FVC), forced expiratory volume in one second (FEV1), maximal expiratory flow rate (MEFR) and maximal mid-expiratory flow (MMEF). Terbutaline caused even more pronounced increases in all four parameters and exhibited a longer duration of action. Neither drug altered arterial pH, arterial oxygen pressure (Pa02), or arterial carbon dioxide pressure (PaCO2). With regard

Acute physiological effects of glucocorticoids on fuel metabolism in humans are permissive but not direct.

Abstract: Background and aims The effects of glucocorticoids on fuel metabolism are complex. Acute glucocorticoid excess promotes lipolysis but chronic glucocorticoid excess causes visceral fat accumulation. We hypothesized that interactions between cortisol and insulin and adrenaline account for these conflicting results. We tested the effect of cortisol on lipolysis and glucose production with and without insulin and adrenaline in humans both in vivo and in vitro. Materials and methods A total of 20 healthy men were randomized to low and high insulin groups (both n = 10). Subjects attended on 3 occasions and received low (c. 150 nM), medium (c. 400 nM) or high (c. 1400 nM) cortisol infusion in a randomized crossover design. Deuterated glucose and glycerol were infused intravenously along with a pancreatic clamp (somatostatin with replacement of glucagon, insulin and growth hormone) and adrenaline. Subcutaneous adipose tissue was obtained for analysis. In parallel, the effect of cortisol on lipolysis was tested in paired primary cultures of human subcutaneous and visceral adipocytes. Results In vivo, high cortisol increased lipolysis only in the presence of high insulin and/or adrenaline but did not alter glucose kinetics. High cortisol increased adipose mRNA levels of ATGL, HSL and CGI-58 and suppressed G0S2. In vitro, high cortisol increased lipolysis in the presence of insulin in subcutaneous, but not visceral, adipocytes. Conclusions The acute lipolytic effects of cortisol require supraphysiological concentrations, are dependent on insulin and adrenaline and are observed only in subcutaneous adipose tissue. The resistance of visceral adipose tissue to cortisol's lipolytic effects may contribute to the central fat accumulation observed with chronic glucocorticoid excess.

Epinephrine promotes COX-2-dependent immune suppression in myeloid cells and cancer tissues.

Abstract: Activation of the sympathetic nervous system (e.g., due to stress) has been implicated in cancer progression and recurrence, but its cancer-promoting effects have been variable between different studies. Here, we report that although catecholamines, mediators of systemic sympathetic activity, display only weak immunosuppressive impact on their own, their combination with inflammatory signals leads to the induction of COX-2 and multiple COX-2-dependent suppressive factors in human myeloid cells and cancer tissues. Human macrophages exposed to epinephrine and TNFα, or macrophages generated in 6day cultures in the presence of epinephrine, expressed high levels of COX-2, IDO and IL-10, and strongly suppressed both the proliferation and IFNγ production of CD8+ T cells. These suppressive effects of epinephrine were counteracted by celecoxib, a selective inhibitor of COX-2 activity, which inhibited the induction of immunosuppressive factors (including the elevated expression of COX-2 itself) and the ability of epinephrine-exposed macrophages to suppress CD8+ T cell responses. The activation of the COX-2/PGE2 system and COX-2-dependent suppressive events were also observed in ex vivo human breast and colon cancer explant cultures and were similarly counteracted by celecoxib. Our preliminary data also indicate elevated COX-2 expression in mammary tumors of chronic stress-exposed mice. The current demonstration of the interplay between inflammation and the induction of immunosuppressive factors by catecholamines suggest a contextual impact of stress, helping to explain variable results of epidemiologic studies of the link between sympathetic activity and cancer progression, and implicating COX-2 blockade as a potential means to mitigate stress-related immune suppression.

Delayed-Onset Digital Ischemia After Local Anesthetic With Epinephrine Injection Requiring Phentolamine Reversal

Abstract: The use of low-dose epinephrine in hand surgery has made it possible to perform a wide range of surgical procedures in the office setting. Low-dose epinephrine use is safe, and its vasoconstrictive effects are reversible with phentolamine. In this report, we present late-onset finger ischemia beginning 3 hours after an ipsilateral carpal tunnel and A1 pulley release of the middle finger anesthetized with local anesthetic and low-dose epinephrine (1:100,000). Finger ischemia lasted 14 hours until rescued with phentolamine injection.

Central Nervous System GLP-1 Receptors Regulate Islet Hormone Secretion and Glucose Homeostasis in Male Rats.

Abstract: The glucagon-like peptide 1 (GLP-1) system plays an important role in blood glucose regulation, in great part through coordinate control of insulin and glucagon secretion. These effects are generally attributed to GLP-1 produced in peripheral sites, principally the intestine. GLP-1 is also produced in hindbrain neurons that signal through GLP-1 receptors (GLP-1rs) expressed in brain regions involved in metabolic regulation. GLP-1 in the central nervous system (CNS) induces satiety, visceral illness, and stress responses. However, recent evidence suggests CNS GLP-1 is also involved in glucose regulation. To test the hypothesis that central GLP-1 regulates islet hormone secretion, conscious rats were given intracerebroventricular (ICV) GLP-1, GLP-1r antagonist exendin-[9-39] (Ex-9), or saline during fasting or hyperglycemia from intravenous glucose. Administration of CNS GLP-1 increased fasting glucose, glucagon, corticosterone, and epinephrine and blunted insulin secretion in response to hyperglycemia. Paradoxically, GLP-1r blockade with ICV Ex-9 also reduced glucose-stimulated insulin secretion, and administration of ICV Ex-9 to freely feeding rats caused mild glucose intolerance. Thus, direct administration of CNS GLP-1 affected islet hormone secretion counter to what is seen with peripherally administered GLP-1, an effect likely due to stimulation of sympathetic nervous system activity. In contrast, blockade of brain GLP-1r supports a role for CNS GLP-1 on glucose-stimulated insulin secretion and glucose control after a meal. These findings suggest a model in which activation of CNS GLP-1r by endogenous peptide promotes glucose tolerance, an effect that can be overridden by stress responses stimulated by exogenous GLP-1.

Acupuncture Attenuates Renal Sympathetic Activity and Blood Pressure via Beta-Adrenergic Receptors in Spontaneously Hypertensive Rats

Abstract: The sympathetic nervous system, via epinephrine and norepinephrine, regulates β-adrenergic receptor (β-AR) expression, and renal sympathetic activation causes sustained increases in blood pressure by enhanced renin release. In this study, we aim to investigate the effect and underlying mechanism of acupuncture at Taichong (LR3) on renal sympathetic activity in spontaneously hypertensive rats. Unanesthetized rats were subject to daily acupuncture for 2 weeks. Mean blood pressure (MBP) and heart rate variability (HRV) were monitored at days 0, 7, and 14 by radiotelemetry. After euthanasia on the 14th day, blood and the kidneys were collected and subject to the following analyses. Epinephrine and norepinephrine were detected by ELISA. The expression of β-ARs was studied by western blotting and PCR. The renin content was analyzed by radioimmunoassay. 14-day acupuncture significantly attenuates the increase of MBP. The HRV indices, the standard deviation of all normal NN intervals (SDNN), and the ratio of the low-frequency component to the high-frequency component (LF/HF) were improved following acupuncture. Renal sympathetic activation induced upregulation of epinephrine, norepinephrine, and renin content were attenuated by acupuncture. In addition, acupuncture decreased β1-AR expression and improved β2-AR expression. These results indicated that acupuncture relieves the increased MBP via the regulation of renal sympathetic activity and β-ARs.

Pitfalls in the use of epinephrine for anaphylaxis: patient and provider opportunities for improvement

Abstract: Background Epinephrine remains the mainstay of treatment for life-threatening allergic reactions. A number of challenges are encountered with epinephrine, resulting in underutilization and misutilization of epinephrine. The purpose of this study was to identify the scope of epinephrine pitfalls and opportunities for improvement in the management of allergy emergencies. Methods A PubMed search from 1990 to 2015 was performed to identify all cases and reports pertaining to the use and misuse of epinephrine for anaphylaxis. Studies were assessed for obstacles or complications related to proper administration of epinephrine for treatment of allergic reactions, and were divided into problems originating with patients compared to healthcare providers. Results There were 1840 publications related to epinephrine use, of which 61 reports met inclusion criteria for pitfalls in the use of epinephrine. The most common problems reported related to lack of autoinjector availability (22), inadequate education of patients or providers (9), uncertainty about when or how to administer epinephrine (9), concern for systemic effects (13), failure to administer (8), and accidental administration (2). Responsibility for errors was divided among patients (18), providers (39), or both (4). Conclusion Epinephrine is a potent medication with lifesaving indications and is the standard of care for treatment of anaphylaxis. The delivery of epinephrine in both trained and untrained populations carries certain pitfalls and complications that can have serious consequences. Identification of the scope of the problem is an important step in improving education for both providers and patients who are tasked with use of epinephrine for allergy emergencies.

Epinephrine Auto-Injector Versus Drawn Up Epinephrine for Anaphylaxis Management: A Scoping Review

Abstract: Objective:Anaphylaxis is a life-threatening event. Most clinical symptoms of anaphylaxis can be reversed by prompt intramuscular administration of epinephrine using an auto-injector or epinephrine drawn up in a syringe and delays and errors may be fatal. The aim of this scoping review is to identify

Myocardial infarction during anaphylaxis in a young healthy male with normal coronary arteries- is epinephrine the culprit?

Abstract: Anaphylaxis is an acute, potentially fatal medical emergency. Myocardial injury or infarction in the setting of an anaphylaxis can be due the anaphylaxis itself, when it is known as Kounis syndrome or it can also be due to the effect of epinephrine treatment. Epinephrine is considered as the cornerstone in management of anaphylaxis. Myocardial infarction secondary to therapeutic doses of adrenaline is a rare occurrence and only a few cases have been reported in literature. The mechanism of myocardial injury was considered to be due to coronary vasospasm secondary to epinephrine as the coronary angiograms were normal on these occasions. A 21-year- old previously healthy male got admitted to the local hospital with an urticarial rash and difficulty in breathing, one hour after ingestion of prawns for which he was known to be allergic. He was treated with 0.5 ml of intramuscular adrenaline (1:1000) which was administered to the lateral side of the thigh, following which he developed palpitations and tightening type central chest pain. Electrocardiogram showed ST segment depressions in leads III, aVF and V1 to V5 and he was transferred to a tertiary care hospital. The second electrocardiogram, done 2 h later, showed resolution of ST segment depressions but new T inversions in leads I and aVL. Troponin I was elevated with a titer of 2.15 ng/ml. He was treated with sublingual GTN in the emergency treatment unit and the symptoms resolved. Transthoracic 2D echocardiogram and stress testing with treadmill was normal and CT coronary angiogram revealed normal coronary arteries. Here we present a case of a young healthy adult with no significant risk factors for coronary artery disease who developed myocardial infarction following intramuscular administration of therapeutic dose of adrenalin for an anaphylactic reaction. The postulated mechanism is most likely an alpha receptor mediated coronary vascular spasm. However the use of adrenaline in the setting of life threatening anaphylaxis is life saving and the benefits far outweigh the risks of adverse effects. Therefore the purpose of reporting this case is not to discourage the use of adrenaline in anaphylaxis but to make aware of this potential adverse effect which can occur in the acute setting.

Endothelial Regulator of Calcineurin 1 Promotes Barrier Integrity and Modulates Histamine-Induced Barrier Dysfunction in Anaphylaxis.

Abstract: Anaphylaxis, the most serious and life-threatening allergic reaction, produces the release of inflammatory mediators by mast cells and basophils. Regulator of calcineurin 1 (Rcan1) is a negative regulator of mast-cell degranulation. The action of mediators leads to vasodilation and an increase in vascular permeability, causing great loss of intravascular volume in a short time. Nevertheless, the molecular basis remains unexplored on the vascular level. We investigated Rcan1 expression induced by histamine, platelet-activating factor (PAF), and epinephrine in primary human vein (HV)-/artery (HA)-derived endothelial cells (ECs) and human dermal microvascular ECs (HMVEC-D). Vascular permeability was analyzed in vitro in human ECs with forced Rcan1 expression using Transwell migration assays and in vivo using Rcan1 knockout mice. Histamine, but neither PAF nor epinephrine, induced Rcan1-4 mRNA and protein expression in primary HV-ECs, HA-ECs, and HMVEC-D through histamine receptor 1 (H1R). These effects were prevented by pharmacological inhibition of calcineurin with cyclosporine A. Moreover, intravenous histamine administration increased Rcan1 expression in lung tissues of mice undergoing experimental anaphylaxis. Functional in vitro assays showed that overexpression of Rcan1 promotes barrier integrity, suggesting a role played by this molecule in vascular permeability. Consistent with these findings, in vivo models of subcutaneous and intravenous histamine-mediated fluid extravasation showed increased response in skin, aorta, and lungs of Rcan1-deficient mice compared with wild-type animals. These findings reveal that endothelial Rcan1 is synthesized in response to histamine through a calcineurin-sensitive pathway and may reduce barrier breakdown, thus contributing to the strengthening of the endothelium and resistance to anaphylaxis. These new insights underscore its potential role as a regulator of sensitivity to anaphylaxis in humans.

Adrenal medullary dysfunction as a feature of obesity.

Abstract: Although there is strong evidence linking obesity with increased sympathoneural activity, involvement of the adrenal medulla is less clear. We therefore investigated adrenal medullary function under fasting and feeding conditions in normal weight (NW, n=33), overweight (OW, n=28) and obese (OB, n=36) adults (59% women). Ninety-seven healthy adults participated in a cross-sectional study with recruitment stratified according to BMI. Plasma for catecholamines and metanephrines was sampled in the fasting state, at 30-min intervals during a 120-min glucose tolerance test and during an euglycaemic-hyperinsulinaemic clamp (40 mU m−2 min−1 insulin dose). Body composition was determined by leg-to-leg bioelectrical impedance analysis. Obese subjects had the lowest fasting plasma concentrations of epinephrine (NW: 0.17, 95% confidence interval (CI): 0.14–0.20 nmol l−1; OW: 0.16, 95% CI: 0.12–0.19 nmol l−1; OB: 0.11, 95% CI: 0.08–0.13 nmol l−1; P=0.018) and metanephrine (NW: 0.17, 95% CI: 0.15–0.19 nmol l−1; OW: 0.15, 95% CI: 0.13–0.16 nmol l−1; OB: 0.13, 95% CI: 0.12–0.15 nmol l−1; P=0.022), the latter reflecting adrenal medullary store size. Fasting plasma epinephrine (r=−0.437; P<0.001) and metanephrine (r=−0.477; P<0.001) concentrations were additionally inversely correlated with whole-body fat percentage. Suppression of epinephrine secretion in response to carbohydrate ingestion was significantly blunted in overweight and obese subjects compared with the normal weight subjects (Pinteraction=0.045). Most of the variance in basal epinephrine was related to whole-body fat percentage (β=−0.389, 95% CI: −0.09 to −0.69; P=0.012) that explained the lower concentrations of epinephrine and metanephrine in women than men. We provide evidence that adrenomedullary dysfunction is a characteristic feature of obesity that involves both reduced adrenal secretion of epinephrine and size of adrenal medullary epinephrine stores.

Hypoperfusion in response to epinephrine in local anaesthetics: Investigation of dependence on epinephrine concentration, spread of hypoperfusion and time to maximal cutaneous vasoconstriction

Abstract: Summary Objectives The present study aimed to examine hypoperfusion in response to epinephrine following the administration of a local anaesthetic. The concentration of epinephrine that causes maximal hypoperfusion, the spread of hypoperfusion in the tissue and the time to the stabilization of hypoperfusion were investigated. Methods Blood perfusion was monitored using laser Doppler velocimetry and laser speckle contrast imaging of random-pattern advancement flaps (1 × 4 cm) or intact skin on the pig flank. Epinephrine was either injected cumulatively (0.1, 1.0, 10 or 100 μg/ml) after injecting 20 mg/ml lidocaine, to determine the concentration response, or given as a single dose (12.5 μg/ml epinephrine + 20 mg/ml lidocaine). Control experiments were performed with saline or lidocaine (without epinephrine). Results Increasing concentrations of epinephrine resulted in a gradual decrease in skin perfusion, approaching a minimum after injecting 10 μg/ml. The area of hypoperfusion was 12 mm in radius, and the time from the injection to the stabilization of hypoperfusion was approximately 120 s. After the administration of 10 μg/ml epinephrine in flaps with small pedicle, 25% blood perfusion still remained. Conclusions Local anaesthetic with an epinephrine concentration of approximately 10 μg/ml appears to be adequate for vasoconstriction before surgery. Incisions were required to be delayed only for 2 min following local anaesthetic with epinephrine in pigs. The remaining 25% blood perfusion observed after the administration of epinephrine supports the use of epinephrine in flaps with a small pedicle. Obviously, these experimental findings must be clinically assessed before being considered for infiltration anaesthesia during plastic surgery procedures.

Evaluating real-time effects of topical 1:1000 epinephrine in endoscopic sinus and skull-base surgery on hemodynamic parameters through intraoperative arterial line monitoring.

Abstract: Background Administration of topical 1:1000 epinephrine is commonly used in practice to achieve vasoconstriction during endoscopic sinus surgery and skull-base surgery; however, real-time effects on cardiovascular changes from systemic absorption have not been well studied. Methods Twenty-six patients undergoing endoscopic transsphenoidal resection of a pituitary lesion at a single institution were included into the study. Following arterial line placement by anesthesiology, 6 cottonoid pledgets soaked in 1:1000 epinephrine were placed into the bilateral nasal passages. Hemodynamic parameters including heart rate, blood pressure, and mean arterial pressure were collected at baseline, 30 seconds, and increments in minutes up to 10 minutes. Additional potentially confounding factors such as use of antihypertensives, stress dose steroids, and positioning with head pins were all performed following termination of data collection. Results The majority of patients (20/26, 77%) showed no significant change in any parameter following placement of epinephrine soaked cottonoids. Six patients, however, had transient increases in blood pressure following administration of topical epinephrine, with a few requiring vasodilatory interventions. Return to baseline cardiovascular values were noted after an average of 7 minutes. There was no correlative preoperative characteristic that predicted sensitivity to placement of epinephrine. There were no lasting or permanent effects. Conclusion Although intranasal topical 1:1000 epinephrine use showed no substantial hemodynamic changes in the majority of patients, in a subset of patients it can cause significant transient elevations in blood pressure to a degree necessitating intervention. Topical epinephrine should be used judiciously in endoscopic sinus surgery.

Epinephrine in Out-of-hospital Cardiac Arrest: Helpful or Harmful?

Abstract: Objective: Epinephrine is the primary drug administered during cardiopulmonary resuscitation (CPR) to reverse cardiac arrest. The evidence for the use of adrenaline in out-of-hospital cardiac arrest (OHCA) and in-hospital resuscitation is inconclusive. We conducted a systematic review on the clinical efficacy of adrenaline in adult OHCA patients to evaluate whether epinephrine provides any overall benefit for patients. Data Sources: The EMBASE and PubMed databases were searched with the key words “epinephrine,” “cardiac arrest,” and variations of these terms. Study Selection: Data from clinical randomized trials, meta-analyses, guidelines, and recent reviews were selected for review. Results: Sudden cardiac arrest causes 544,000 deaths in China each year, with survival occurring in Conclusions: The administration of adrenaline was associated with improved short-term survival (ROSC). However, it appears that the use of adrenaline is associated with no benefit on survival to hospital discharge or survival with favorable neurological outcome after OHCA, and it may have a harmful effect. Larger placebo-controlled, double-blind, randomized control trials are required to definitively establish the effect of epinephrine.

Monitoring the Secretory Behavior of the Rat Adrenal Medulla by High-Performance Liquid Chromatography-Based Catecholamine Assay from Slice Supernatants

Abstract: Catecholamine secretion from the adrenal medullary tissue is a key step of the adaptive response triggered by an organism to cope with stress Whereas molecular and cellular secretory processes have been extensively studied at the single chromaffin cell level, data available for the whole gland level are much scarcer We tackled this issue in rat by developing an easy to implement experimental strategy combining the adrenal acute slice supernatant collection with a high performance liquid chromatography-based epinephrine and norepinephrine assay This technique affords a convenient method for measuring basal and stimulated catecholamine release from single acute slices, allowing thus to individually address the secretory function of the left and right glands Our data point that the two glands are equally competent to secrete epinephrine and norepinephrine, exhibiting an equivalent epinephrine:norepinephrine ratio, both at rest and in response to a cholinergic stimulation Nicotine is however more efficient than acetylcholine to evoke norepinephrine release A pharmacological challenge with hexamethonium, an α3-containing nicotinic acetylcholine receptor antagonist, disclosed that epinephrine- and norepinephrine-secreting chromaffin cells distinctly expressed α3 nicotinic receptors, with a dominant contribution in norepinephrine cells As such, beyond the novelty of catecholamine assays from acute slice supernatants, our study contributes at refining the secretory behavior of the rat adrenal medullary tissue, and opens new perspectives for monitoring the release of other hormones and transmitters, especially those involved in the stress response

Use of Epinephrine in Patients with Drug-Induced Anaphylaxis: An Analysis of the Beijing Pharmacovigilance Database.

Abstract: Background: Few studies assessing the use of epinephrine in drug-induced anaphylaxis (DIA) in the hospital setting are available. We utilized the Beijing Pharmacovigilance Database (BPD) to evaluate the appropriateness of epinephrine for DIA management. Methods: DIA cases collected in the BPD from January 2004 to December 2014 were adjudicated and analyzed for demographics, causative drugs, clinical signs, outcomes, initial treatment, route, dosing, and cardiovascular adverse events (CAE) of epinephrine. Results: DIA was primarily caused by antibiotics (38.4%), radiocontrast agents (11.9%), traditional Chinese medicine injections (10.9%), and chemotherapeutic drugs (10.3%). Only 708 (59.5%) patients received epinephrine treatment. Patients who received epinephrine were more likely to experience wheezing (p < 0.001) and respiratory arrest (p < 0.001). Among 518 patients with a complete record of the epinephrine administration route, the percentage of patients receiving it by intramuscular (IM) injection, subcutaneous (SC) injection, intravenous (IV) bolus injection, or IV continuous infusion was 16.9, 31.5, 43.5, and 8.1%, respectively. Among the 427 patients with a record of both the administration route and the dosing, an overdose was more likely with IV bolus (94.1%) in contrast to IM injection (56.6%; p < 0.001) or SC injection (43.7%; p < 0.001). Among the patients analyzed for CAE (n = 349), 17 patients accounted for 19 CAE, and 13 (76.5%) of these patients were overdosed with epinephrine. Conclusion: Underuse, inappropriate IV bolus use, and overdosing were the 3 major problems with epinephrine use in DIA in China. Educational training for health care professionals on the appropriate use of epinephrine in managing anaphylactic reactions is suggested.

Emergency Medicine Myths: Epinephrine in Cardiac Arrest.

Abstract: Background Sudden cardiac arrest accounts for approximately 15% of deaths in developed nations, with poor survival rate. The American Heart Association states that epinephrine is reasonable for patients with cardiac arrest, though the literature behind its use is not strong. Objective To review the evidence behind epinephrine for cardiac arrest. Discussion Sudden cardiac arrest causes over 450,000 deaths annually in the United States. The American Heart Association recommends epinephrine may be reasonable in patients with cardiac arrest, as part of Advanced Cardiac Life Support. This recommendation is partly based on studies conducted on dogs in the 1960s. High-dose epinephrine is harmful and is not recommended. Epinephrine may improve return of spontaneous circulation, but does not improve survival to discharge or neurologic outcome. Literature suggests that three phases of resuscitation are present: electrical, circulatory, and metabolic. Epinephrine may improve outcomes in the circulatory phase prior to 10 min post arrest, though further study is needed. Basic Life Support measures including adequate chest compressions and early defibrillation provide the greatest benefit. Conclusions Epinephrine may improve return of spontaneous circulation, but it does not improve survival to discharge or neurologic outcome. Timing of epinephrine may affect patient outcome, but Basic Life Support measures are the most important aspect of resuscitation and patient survival.

Effect of Prenatal and Postnatal Exposure to Low Doses of DDT on Catecholamine Secretion in Rats in Different Period of Ontogeny.

Abstract: We studied the effects of prenatal and postnatal exposure to low doses of DDT on secretion of basic catecholamines epinephrine and norepinephrine in pubertal and adult rats. It was found that the endocrine-disrupting chemical under study led to a progressive decrease in the content of epinephrine and especially norepinephrine in systemic circulation, which indicated their disturbed secretion by the adrenal medulla and sympathetic nervous system cells. In animals exposed to low doses of DDT in both pre- and postnatal periods, the decrease in catecholamine secretion after puberty was less pronounced than in animals exposed only during the postnatal period, which can indicate the development of compensatory processes.

Epinephrine but not vasopressin attenuates the airway response to anaphylactic shock in rats.

Abstract: Purpose: The two life-threatening signs of anaphylactic shock (AS) are severe arterial hypotension and bronchospasm Guidelines recommend epinephrine as first-line treatment Arginine vasopressin (AVP) has been proposed as an alternative if epinephrine does not correct arterial hypotension These two drugs may have beneficial, neutral or deleterious effects on airflow either directly or by modifying factors that regulate vasodilatation and/or edema in the bronchial wall Aim of the Study: To compare the effects of epinephrine and AVP on airflow and airway leakage in a rat model of AS Materials and Methods: Thirty-two ovalbumin-sensitized rats were randomized into four groups: control (CON), AS without treatment (OVA), AS treated with epinephrine (EPI), and AS treated with AVP (AVP) Mean arterial pressure (MAP), respiratory resistance and elastance and microvascular leakage in the airways were measured Results: All OVA rats died within 20 minutes following ovalbumin injection Ovalbumin induced

Effects of Epinephrine on Inflammation-Related Gene Expressions in Cultured Rat Cardiomyocytes.

Abstract: Epinephrine, a non-specific adrenergic agonist, is one of the most commonly used inotropes perioperatively. Recent studies have shown that inflammatory response in cardiac surgery could result in hypoperfusion, dysrhythmias, myocardial ischemia, and other pathophysiological alterations in the postoperative period. These alterations might be contributing to the adverse clinical outcome. Although epinephrine has been shown to have effects on the immune system, how epinephrine affects inflammatory response is unclear. We hypothesized that epinephrine exposure may alter the inflammatory response which may potentially contribute to the adverse clinical outcomes. We used cultured rat cardiomyocytes (H9C2) with epinephrine exposure in this study. The expression of mRNA for inflammation-related genes was quantitated for the comparison of experimental group (with epinephrine) and control group (without epinephrine). The results demonstrated significant changes of inflammation-related gene expressions in cardiomyocytes after epinephrine administration. The clinical implications of the gene expression changes in cardiomyocytes are unclear.