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Showing papers on "Epinephrine published in 2014"


OtherDOI
TL;DR: The present knowledge of the effects of circulating catecholamines on peripheral organs and tissues, as well as on memory in the brain are discussed, with a focus on the "fight-or-flight" response.
Abstract: Physical challenges, emotional arousal, increased physical activity, or changes in the environment can evoke stress, requiring altered activity of visceral organs, glands, and smooth muscles. These alterations are necessary for the organism to function appropriately under these abnormal conditions and to restore homeostasis. These changes in activity comprise the "fight-or-flight" response and must occur rapidly or the organism may not survive. The rapid responses are mediated primarily via the catecholamines, epinephrine, and norepinephrine, secreted from the adrenal medulla. The catecholamine neurohormones interact with adrenergic receptors present on cell membranes of all visceral organs and smooth muscles, leading to activation of signaling pathways and consequent alterations in organ function and smooth muscle tone. During the "fight-or-flight response," the rise in circulating epinephrine and norepinephrine from the adrenal medulla and norepinephrine secreted from sympathetic nerve terminals cause increased blood pressure and cardiac output, relaxation of bronchial, intestinal and many other smooth muscles, mydriasis, and metabolic changes that increase levels of blood glucose and free fatty acids. Circulating catecholamines can also alter memory via effects on afferent sensory nerves impacting central nervous system function. While these rapid responses may be necessary for survival, sustained elevation of circulating catecholamines for prolonged periods of time can also produce pathological conditions, such as cardiac hypertrophy and heart failure, hypertension, and posttraumatic stress disorder. In this review, we discuss the present knowledge of the effects of circulating catecholamines on peripheral organs and tissues, as well as on memory in the brain.

182 citations


Journal ArticleDOI
TL;DR: Wasp and bee venom, legumes, animal proteins, and analgesic drugs were the commonest triggers of anaphylaxis and Epinephrine was given too rarely, as it is recommended in the guidelines for all cases of grade 2 and above.
Abstract: Anaphylaxis is defined as an acute systemic reaction with the symptoms of an immediate allergic reaction that can affect the entire organism and is potentially life-threatening (1– 3). Anaphylaxis can be fatal or lead to permanent damage (3). Pathophysiologically, anaphylactic reactions—especially those triggered by foods or insect venom—are predominantly IgE-mediated, but in rare cases direct activation of the mast cells can be the cause. At present no uniform worldwide definition of anaphylaxis exists. A mechanistic approach uses the term “anaphylaxis” for systemic generalized reactions of all degrees of severity (4). The definition most often used today describes anaphylaxis as a severe generalized reaction with symptoms in various organ systems (skin and mucosa, respiratory tract, cardiovascular system, gastrointestinal tract) (5). The differential diagnosis of anaphylaxis includes a large number of possible conditions (Box). Box Differential diagnoses of anaphylaxis Cardiovascular events Vasovagal syncope Other forms of shock (e.g., hemorrhagic, cardiogenic) Cardiac arrhythmias Hypertensive crisis Pulmonary embolism Capillary leak syndrome Endocrinological/metabolic events Carcinoid syndrome Pheochromocytoma Thyrotoxic crisis Hypoglycemia Psychogenic events Hyperventilation, especially with globus hystericus attacks Multiple chemical sensitivity (MCS) Munchhausen syndrome (anaphylaxis as artifact) Cerebral events Epilepsy Stroke Coma (without anaphylaxis), e.g., metabolic, traumatic Airway events Vocal cord dysfunction, psychogenic respiratory distress Tracheal/bronchial obstruction (e.g., foreign body, tumor) Asthma (without anaphylaxis) Pharmacological/toxic events Due to drugs (e.g., local anesthetic i.v.) Due to alcohol and administration of substances that cause a disulfiram-like reaction (e.g., griseofulvin, sulfonyl ureas, certain fungal toxins) (Modified from Ring et al. [12])

156 citations


Journal ArticleDOI
TL;DR: In this large cohort of patients who achieved ROSC, pre-hospital use of epinephrine was consistently associated with a lower chance of survival, an association that showed a dose effect and persisted despite post-resuscitation interventions.

124 citations


Journal ArticleDOI
TL;DR: In this article, the effect of glucocorticoid receptor (GCR) and β2-adrenergic receptor (β2-AR) on leukocyte subpopulations was quantified by flow cytometry.
Abstract: Infectious complications are the leading cause of death in the post-acute phase of stroke. Post-stroke immunodeficiency is believed to result from neurohormonal dysregulation of the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis. However, the differential effects of these neuroendocrine systems on the peripheral immune cells are only partially understood. Here, we determined the impact of the hormones of the SNS and HPA on distinct immune cell populations and characterized their interactions after stroke. At various time points after cortical or extensive hemispheric cerebral ischemia, plasma cortisone, corticosterone, metanephrine and adrenocorticotropic hormone (ACTH) levels were measured in mice. Leukocyte subpopulations were flow cytometrically analyzed in spleen and blood. To investigate their differential sensitivity to stress hormones, splenocytes were incubated in vitro with prednisolone, epinephrine and their respective receptor blockers. Glucocorticoid receptor (GCR) and beta2-adrenergic receptor (β2-AR) on leukocyte subpopulations were quantified by flow cytometry. In vivo effects of GCR and selective β2-AR blockade, respectively, were defined on serum hormone concentrations, lymphopenia and interferon-γ production after severe ischemia. We found elevated cortisone, corticosterone and metanephrine levels and associated lymphocytopenia only after extensive brain infarction. Prednisolone resulted in a 5 times higher cell death rate of splenocytes than epinephrine in vitro. Prednisolone and epinephrine-induced leukocyte cell death was prevented by GCR and β2-AR blockade, respectively. In vivo, only GCR blockade prevented post ischemic lymphopenia whereas β2-AR preserved interferon-γ secretion by lymphocytes. GCR blockade increased metanephrine levels in vivo and prednisolone, in turn, decreased β2-AR expression on lymphocytes. In conclusion, mediators of the SNS and the HPA axis differentially affect the systemic immune system after stroke. Moreover, our findings suggest a negative-feedback of corticosteroids on the sympathetic axis which may control the post-stroke stress-reaction. This complex interplay between the HPA and the SNS after stroke has to be considered when targeting the neurohormonal systems in the post acute phase of severe stroke.

112 citations


Journal ArticleDOI
TL;DR: It is demonstrated that epinephrine alters the neutrophil (PMN)-dependent inflammatory response to a cutaneous wound and that β2 adrenergic receptor-dependent activation of pro-inflammatory macrophages is critical forEpinephrine-mediated IL-6 production.

91 citations


Journal ArticleDOI
TL;DR: Catecholamine-induced takotsubo-like cardiac dysfunction appears to be afterload dependent rather than depend on stimulation of a specific adrenergic receptor subtype.

87 citations


Journal ArticleDOI
TL;DR: The improved ICD-10 coding defines the different symptoms and types of anaphylaxis and includes coding for anphylaxis without shock, consistent with the efforts of the National Institute of Allergy and Infectious Diseases (NIAID) and the FAAN, who convened a panel to formulate a definition of and the diagnostic criteria for anAPHylaxis.

77 citations


Journal ArticleDOI
TL;DR: The findings markedly limit the significance of stress/surgery-induced corticosterone release in the in vivo suppression of NKCC, and highlight the blockade of epinephrine or/and prostaglandins as effective and clinically feasible approaches to overcome such immuno-suppressive effects.
Abstract: Most in vitro and ex-vivo studies indicate a profound suppression of NK cell cytotoxicity (NKCC) by glucocorticoids; while catecholamines and prostaglandins were reported both to suppress and to enhance NKCC. However, methodological considerations hinder our ability to deduce from these findings to the impact of endogenous release of these factors on in vivo levels of NKCC and their implications to NK-dependent resistance to pathologies in living humans or animals. Here we used an in vivo approach that sensitively and specifically reflects NKCC in living F344 rats, based on lung clearance of NK-sensitive tumor cells (MADB106), and based on comparing effects between NK-intact and NK-depleted rats. To study the role of corticosterone, epinephrine, and prostaglandins, we administered these factors to rats, or antagonized their endogenous release following different stress paradigms or surgery. The results indicated that endogenous or exogenous elevated corticosterone levels can suppress in vivo NKCC levels, but only under some conditions, and mostly secondarily to the NK-suppressing impact of epinephrine. Specifically, corticosterone-induced NKCC suppression occurred (i) only under prolonged, but not short exposure to stress, and mainly in males; (ii) was smaller than the prominent impact of epinephrine; (iii) was mostly ascribed to corticosterone-induced potentiation of the effects of epinephrine or/and prostaglandins; and (iv) was completely abolished through antagonizing epinephrine or/and prostaglandins. Overall, these findings markedly limit the significance of stress/surgery-induced corticosterone release in the in vivo suppression of NKCC, and highlight the blockade of epinephrine or/and prostaglandins as effective and clinically feasible approaches to overcome such immuno-suppressive effects.

61 citations


Journal ArticleDOI
TL;DR: Restoration of adrenal α2AR signaling through the inhibition of GRK2 is a fascinating sympatholytic therapeutic strategy for chronic HF and could have several significant advantages over existing HF pharmacotherapies minimizing side-effects on extra-cardiac tissues and reducing the chronic activation of the renin–angiotensin–aldosterone and endothelin systems.
Abstract: Heart failure (HF) is a chronic clinical syndrome characterized by the reduction in left ventricular (LV) function and it represents one of the most important causes of morbidity and mortality worldwide. Despite considerable advances in pharmacological treatment, HF represents a severe clinical and social burden. Sympathetic outflow, characterized by increased circulating catecholamines (CAs) biosynthesis and secretion, is peculiar in HF and sympatholytic treatments (as β-blockers) are presently being investigated for the treatment of this disease. Adrenal gland secretes Epinephrine (80%) and Norepinephrine (20%) in response to acetylcholine stimulation of nicotinic cholinergic receptors on the chromaffin cell membranes. This process is regulated by adrenergic receptors (ARs): α2ARs inhibit CA release through coupling to inhibitory Gi-proteins, and βARs (mainly β2ARs) stimulate CA release through coupling to stimulatory Gs-proteins. All ARs are G-protein-coupled receptors (GPCRs) and GPCR kinases (GRKs) regulate their signaling and function. Adrenal GRK2-mediated α2AR desensitization and downregulation are increased in HF and seem to be a fundamental regulator of CA secretion from the adrenal gland. Consequently, restoration of adrenal a2AR signaling through the inhibition of GRK2 is a fascinating sympatholytic therapeutic strategy for chronic HF. This strategy could have several significant advantages over existing HF pharmacotherapies (antiadrenergic, such as bAR-blockers) minimizing side-effects on extra-cardiac tissues and reducing the chronic activation of the renin–angiotensin–aldosterone and endothelin systems. The role of adrenal ARs in regulation of sympathetic hyperactivity opens interesting perspectives in understanding pathophysiology of HF and identifying new potential therapeutic targets.

47 citations


Journal ArticleDOI
Paul E. Gold1
TL;DR: A mechanism underlying modulation of memory that integrates the physiological functions of multiple organ systems to support brain processes is revealed.

46 citations


Journal ArticleDOI
TL;DR: Less frequent average epinephrine dosing than recommended by consensus guidelines was associated with improved survival of in-hospital cardiac arrest, consistent for both shockable and non-shockable cardiac arrest rhythms.

Journal ArticleDOI
TL;DR: Recurrent hypoglycemia impairs counterregulatory (CR) hormone responses to subsequent hypoglycesmia.
Abstract: Tight glycemic control of type 1 diabetes mellitus (T1DM) reduces the development and slows the progression of diabetes-related microvascular complications (1) and may reduce the development and progression of macrovascular complications (2). However, tight glycemic control increases the frequency of recurrent symptomatic and severe hypoglycemia (1). Indeed hypoglycemia continues to be a fact of life for people with T1DM (3) who suffer untold numbers of episodes of asymptomatic hypoglycemia. Population-based data (4, 5) indicate that patients with T1DM suffer an average of 1–3 episodes of severe, at least temporarily disabling, hypoglycemia per year. These episodes can be fatal (6). Decreasing plasma glucose concentrations within and just below the post-absorptive physiological range (approximately 70 to 110 mg/dL) normally signal a series of hormonal and symptom responses that protect against hypoglycemia (3, 7). In non-diabetic individuals, these responses include: 1) a decrease in insulin secretion at glucose levels of 80–85 mg/dL, 2) increases in the secretion of glucose counterregulatory hormones including glucagon (GON) and epinephrine (EPI) at glucose levels of 65–70 mg/dL, and 3) neurogenic (autonomic) as well as neuroglycopenic symptoms at glucose levels of 50–55 mg/dL. In diabetic patients with absolute endogenous insulin deficiency (T1DM or advanced T2DM), decrements in insulin and increments in glucagon in response to falling glucose or hypoglycemia are lost and increments in adrenomedullary epinephrine and sympathetic neural activity are typically attenuated as glucose levels fall in response to therapeutic hyperinsulinemia. The loss of these responses leads to hypoglycemia-associated autonomic failure (HAAF) in diabetes, which posits that episodes of iatrogenic hypoglycemia cause both the clinical syndrome of defective glucose counterregulation (by attenuating the epinephrine response to hypoglycemia in the setting of absent insulin and glucagon responses) and impaired awareness of hypoglycemia (largely by reducing the sympathetic neural response). This in turn causes a vicious cycle of recurrent hypoglycemia (3, 7, 8). Loss of the glucagon response to hypoglycemia in patients with T1DM, first reported by Gerich and colleagues in adults in 1973 (9), was shown to develop relatively early in the course of T1DM. In the study of Bolli et al (10) the glucagon response to hypoglycemia in adults with T1DM began to decrease after about two years of diabetes. Attenuation of the epinephrine response to hypoglycemia was shown by Bolli et al (10) and White et al (8) ten years later. Children with new-onset (duration 5–6 days) T1DM were found to have a reduced plasma glucagon response to hypoglycemia induced by bolus insulin injection but the nadir plasma glucose concentrations tended to be higher in these new-onset patients than in the non-diabetic control subjects (11). This finding of a reduced plasma epinephrine response to hypoglycemia in these new onset patients suggests that this apparent difference in glucose nadirs, though not significantly different, may have been biologically important. Recently, Siafarikas et al, (12) demonstrated a reduced glucagon response, but not a reduced epinephrine response, to hypoglycemia in patients with a duration of T1DM ranging from 1 month to 10 years, and a mean duration of T1DM of 1.9 years. In this study, we tested the hypothesis that glucagon, but not epinephrine, responses to insulin-induced hypoglycemia are blunted in adolescents with T1DM of less than 1-year duration. We document an attenuated glucagon but not epinephrine response to hypoglycemia in the first year of T1DM.

Journal ArticleDOI
07 Apr 2014-BMJ
TL;DR: It is concluded that adrenaline is associated with improved short term survival compared with placebo, but no long term survival benefit was seen, and meta-analysis found no significant effect on longterm survival in randomised trials.
Abstract: Adrenaline (epinephrine) has been an integral component of advanced resuscitation algorithms since the early 1960s. Initial guidelines for the treatment of cardiac arrest recommended the use of intracardiac adrenaline (0.5 mg) or high dose intravenous adrenaline (10 mg), repeating with larger doses if required.1 The mechanism of action for adrenaline in cardiac arrest is attributed to stimulation of α2 receptors in vascular smooth muscle, causing vasoconstriction. This increases aortic diastolic pressure, which in turn leads to increased coronary perfusion pressures, which improves short term survival. Experimental studies, however, suggest that adrenaline impairs cerebral macrovascular2 and microvascular blood flow,3 4 increases ventricular arrhythmias, and increases myocardial dysfunction after return of spontaneous circulation.5 This creates the paradox of better short term survival but at the potential cost of worse long term outcomes. We searched Medline, Embase, the Cochrane Library, and trial registries for systematic reviews, randomised controlled trials, and observational studies relating to the use of adrenaline in the treatment of cardiac arrest. A systematic review linked to the International Liaison Committee for Resuscitation 2010 evidence appraisal of vasoactive drugs in the treatment of cardiac arrest6 identified 53 articles, of which five compared adrenaline with placebo (three randomised trials6 7 8 and two observational studies9 10). The review concluded that adrenaline is associated with improved short term survival compared with placebo, but no long term survival benefit was seen. A more recent systematic review,11 which focused solely on adrenaline in cardiac arrest, identified 10 studies (two randomised trials6 8 and eight observational studies9 10 12 13 14 15 16 17). Meta-analysis found no significant effect on long term survival in randomised trials (odds …

Journal ArticleDOI
TL;DR: These findings present new insights into hypertension and chronic kidney diseases and investigate whether renalase expression is induced by epinephrine via a-adrenoceptor/NFκB pathways in renal proximal tubular epithelial cells.
Abstract: Background/Aims : Renalase is a recently discovered, kidney-specific monoamine oxidase that metabolizes circulating catechola

Journal ArticleDOI
Torill Berg1
TL;DR: In this article, the authors tested the hypothesis that β-adrenoceptors may function as presynaptic, release-facilitating auto-receptors, and showed that β1AR-selective β-blockers reduced norepinephrine overflow to plasma equally efficient as β2ARselective (ICI-118551) and β1+2AR (nadolol) antagonists in both strains.
Abstract: Peripheral norepinephrine release is facilitated by presynaptic β-adrenoceptors (AR), believed to involve the β2-subtype exclusively. However, β1-selective blockers are the most commonly used β-blockers in hypertension. Here I tested the hypothesis that β1AR may function as presynaptic, release-facilitating auto-receptors. Since β1AR-blockers are injected during myocardial infarction, their influence on the cardiovascular response to acute norepinephrine release was also studied. By a newly established method, using tyramine-stimulated release through the norepinephrine transporter (NET), presynaptic control of catecholamine release was studied in normotensive and spontaneously hypertensive rats. β1AR-selective antagonists (CGP20712A, atenolol, metoprolol) reduced norepinephrine overflow to plasma equally efficient as β2AR-selective (ICI-118551) and β1+2AR (nadolol) antagonists in both strains. Neither antagonist lowered epinephrine secretion. Atenolol, which does not cross the blood-brain barrier, reduced norepinephrine overflow after adrenalectomy, adrenalectomy+ganglion blockade, losartan or nephrectomy. Atenolol and metoprolol reduced resting cardiac work load. During tyramine-stimulated norepinephrine release, they had little effect on work load, and increased the transient rise in total peripheral vascular resistance, particularly atenolol when combined with losartan. In conclusion, β1AR, like β2AR, stimulated norepinephrine but not epinephrine release, independent of adrenal catecholamines, ganglion transmission, or renal renin release/angiotensin AT1-receptor activation. β1AR therefore functioned as a peripheral, presynaptic, facilitating auto-receptor. Like tyramine, hypoxia may induce NET-mediated release. Augmented tyramine-induced vasoconstriction, as observed after injection of β1AR-blocker, particularly atenolol combined with losartan, may hamper organ perfusion, and may have clinical relevance in hypoxic conditions such as myocardial infarction.

Journal ArticleDOI
TL;DR: It is demonstrated for the first time that infants with classical CAH due to 21-hydroxylase deficiency have significantly lower plasma epinephrine levels than controls, indicating that impaired adrenomedullary function may occur during fetal development and be present from birth.
Abstract: Context: Classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency can cause life-threatening adrenal crises as well as severe hypoglycemia, especially in very young children. Studies of CAH patients 4 years old or older have found abnormal morphology and function of the adrenal medulla and lower levels of epinephrine and glucose in response to stress than in controls. However, it is unknown whether such adrenomedullary abnormalities develop in utero and/or exist during the clinically high-risk period of infancy and early childhood. Objective: The objective of the study was to characterize adrenomedullary function in infants with CAH by comparing their catecholamine levels with controls. Design/Settings: This was a prospective cross-sectional study in a pediatric tertiary care center. Main Outcome Measures: Plasma epinephrine and norepinephrine levels were measured by HPLC. Results: Infants with CAH (n = 9, aged 9.6 ± 11.4 d) had significantly lower epinephrine levels than controls [...

Journal ArticleDOI
TL;DR: It is concluded that the epinephrine release from the adrenal medulla during IH suppresses insulin secretion causing hyperglycemia, and improves glucose tolerance in mice exposed to IH, and attenuated the impairment in basal and glucose-stimulated insulin secretion.

Journal ArticleDOI
TL;DR: The present evidence for discriminative reactivity of AMPK-expressing medullary catecholamine neurons to the screened energy substrate lactate implies that that lactoprivation is selectively signaled to the hypothalamus by A2 noradrenergic and C1 adrenergic cells.

Journal ArticleDOI
TL;DR: Vasopressin results in improved survival, lower postresuscitation troponin, and less hemodynamic compromise after CA in newborn piglets.
Abstract: Vasopressin improves survival compared with epinephrine in a neonatal piglet model of asphyxial cardiac arrest

Journal ArticleDOI
TL;DR: The effects of two haemoglobin‐derived peptides are investigated on this bombesin‐induced response to noradrenaline and adrenaline in the rat.
Abstract: Background and Purpose Haemopressin and RVD-haemopressin, derived from the haemoglobin α-chain, are bioactive peptides found in brain and are ligands for cannabinoid CB1 receptors. Activation of brain CB1 receptors inhibited the secretion of adrenal catecholamines (noradrenaline and adrenaline) induced by i.c.v. bombesin in the rat. Here, we investigated the effects of two haemoglobin-derived peptides on this bombesin-induced response Experimental Approach Anaesthetised male Wistar rats were pretreated with either haemoglobin-derived peptide, given i.c.v., 30 min before i.c.v. bombesin and plasma catecholamines were subsequently measured electrochemically after HPLC. Direct effects of bombesin on secretion of adrenal catecholamines were examined using bovine adrenal chromaffin cells. Furthermore, activation of haemoglobin α-positive spinally projecting neurons in the rat hypothalamic paraventricular nucleus (PVN, a regulatory centre of central adrenomedullary outflow) after i.c.v. bombesin was assessed by immunohistochemical techniques. Key Results Bombesin given i.c.v. dose-dependently elevated plasma catecholamines whereas incubation with bombesin had no effect on spontaneous and nicotine-induced secretion of catecholamines from chromaffin cells. The bombesin-induced increase in catecholamines was inhibited by pretreatment with i.c.v. RVD-haemopressin (CB1 receptor agonist) but not after pretreatment with haemopressin (CB1 receptor inverse agonist). Bombesin activated haemoglobin α-positive spinally projecting neurons in the PVN. Conclusions and Implications The haemoglobin-derived peptide RVD-haemopressin in the brain plays an inhibitory role in bombesin-induced activation of central adrenomedullary outflow via brain CB1 receptors in the rat. These findings provide basic information for the therapeutic use of haemoglobin-derived peptides in the modulation of central adrenomedullary outflow.

Journal ArticleDOI
TL;DR: The results indicated that corticosterone and prostaglandins are prominent mediators of the IL-12-suppressing effects of stress and surgery, apparently through directly suppressing leukocyte IL- 12 production.

Journal ArticleDOI
TL;DR: The most important management consideration is avoiding treatment delays, because symptoms can progress rapidly and underdiagnosis of anaphylaxis can lead to delayed use of appropriate first-line epinephrine in favor of treatments that should be used as adjunctive only.

Journal ArticleDOI
TL;DR: A contribution of the α-adrenergic pathway to the pathogenesis of catecholamine-induced arrhythmia is identified and α-Blockade emerges as an effective therapy in the murine model of CPVT2 and should be tried in humans resistant to β-blockers.

Journal ArticleDOI
TL;DR: The association of EMS administration of epinephrine with respiratory symptoms, fulfillment of anaphylaxis diagnostic criteria, and low rate of additional epine Adrenaline administration in the ED suggest that ALS EMS administered epinphrine based on symptom severity.
Abstract: Background Anaphylaxis is a potentially life-threatening allergic reaction that may require emergency medical system (EMS) transport. Fatal anaphylaxis is associated with delayed epinephrine administration. Patient outcome data to assess appropriateness of EMS epinephrine administration are sparse. Objectives The objectives of this study are to (1) determine the frequency of epinephrine administration in EMS-transported patients with allergic complaints, (2) identify predictors of epinephrine administration, and (3) determine frequency of emergency department (ED) epinephrine administration after EMS transport. Methods A cohort study was conducted from over 5 years. A total of 59187 EMS transports of an Advanced Life Support (ALS) ambulance service were studied. Results One hundred and three patient transports for allergic complaints were analyzed. Fifteen patients received EMS epinephrine, and epinephrine was recommended for 2 additional patients who refused, for a total of 17 (17%) patients for whom epinephrine was administered or recommended. Emergency medical system epinephrine administration or recommendation was associated with venom as a trigger (29% vs 8%; odds ratio [OR], 4.70; 95% confidence interval [CI], 1.28-17.22; P = .013), respiratory symptoms (88% vs 52%; OR, 6.83; 95% CI, 1.47-31.71; P = .006), and fulfillment of anaphylaxis diagnostic criteria (82% vs 49%; OR, 3.50; 95% CI, 0.94-13.2; P = .0498). Four (4%) patients received epinephrine after ED arrival. Conclusion Low rates of epinephrine administration were observed. The association of EMS administration of epinephrine with respiratory symptoms, fulfillment of anaphylaxis diagnostic criteria, and low rate of additional epinephrine administration in the ED suggest that ALS EMS administered epinephrine based on symptom severity. Additional studies of EMS anaphylaxis management including ED management and outcomes are needed.

Journal ArticleDOI
TL;DR: This study shows the substantial benefits of vasoconstrictors in dental infiltration anesthesia by means of prolonged and deeper therapeutic effect in a dose-dependent manner and a safe anesthesia is possible even when utilizing agents with reduced amount of epinephrine.
Abstract: The aims of this study were to compare and evaluate the clinical anesthetic efficacy of five 4 % articaine solutions with and without epinephrine in pulpal anesthesia after infiltration. In a randomized, double-blinded, crossover study, ten volunteers received local anesthesia infiltration in the maxillary right central incisor with five different solutions (4 % articaine + epinephrine 1:100,000, + epinephrine 1:200,000, + epinephrine 1:300,000, + epinephrine 1:400,000, without epinephrine). Electronic pulp tester was used to calculate the onset, utilization time, time to recede, and the surface integral under the time–effect curve. Additionally, cardiovascular parameters and post-experimental soft tissue anesthesia were examined. Onset as well as time to recede was not influenced by the epinephrine concentration. When using the epinephrine-free agent, time to recede was significantly shorter. Upon decreasing epinephrine concentration, duration of pulpal anesthesia and total anesthetic efficacy declined. The shortest time of anesthesia and lowest anesthetic efficacy were seen for the solution without epinephrine. No association was found between the local anesthetic drug and cardiovascular parameters. Soft tissue anesthesia was significantly shorter without epinephrine. This study shows the substantial benefits of vasoconstrictors in dental infiltration anesthesia. These findings were reflected by means of prolonged and deeper therapeutic effect in a dose-dependent manner. Even when utilizing agents with reduced amount of epinephrine, a safe anesthesia is possible. The epinephrine-free solutions resulted in a distinct limitation of utilization time and efficacy.

Journal ArticleDOI
TL;DR: Epinephrine alone or in combination with lipid was associated with an increased number of ECG abnormalities compared with lipid emulsion alone, and Lipid emulsion with or without epinephrine, or epinphrine alone were equally effective in achieving a return to spontaneous circulation in this model of LAST.
Abstract: Background The optimal dosing regimens of lipid emulsion, epinephrine, or both are not yet determined in neonates in cases of local anaesthetic systemic toxicity (LAST). Methods Newborn piglets received levobupivacaine until cardiovascular collapse occurred. Standard cardiopulmonary resuscitation was started and electrocardiogram (ECG) was monitored for ventricular tachycardia, fibrillation, or QRS prolongation. Piglets were then randomly allocated to four groups: control (saline), Intralipid ® alone, epinephrine alone, or a combination of Intralipd plus epinephrine. Resuscitation continued for 30 min or until there was a return of spontaneous circulation (ROSC) accompanied by a mean arterial pressure at or superior to the baseline pressure and normal sinus rhythm for a period of 30 min. Results ROSC was achieved in only one of the control piglets compared with most of the treated piglets. Mortality was not significantly different between the three treatment groups, but was significantly lower in all the treatment groups compared with control. The number of ECG abnormalities was zero in the Intralipid only group, but 14 and 17, respectively, in the epinephrine and epinephrine plus lipid groups ( P Conclusions Lipid emulsion with or without epinephrine, or epinephrine alone were equally effective in achieving a return to spontaneous circulation in this model of LAST. Epinephrine alone or in combination with lipid was associated with an increased number of ECG abnormalities compared with lipid emulsion alone.


Journal ArticleDOI
TL;DR: Epinephrine is crucial for β2-adrenoceptor–mediated vasodilation and facilitation of norepinephrine release in the aorta of phenylethanolamine-N-methyltransferase–knockout mice, and was supported by immunofluorescence confocal microscopy.
Abstract: It has been suggested that there is a link between epinephrine synthesis and the development of β 2-adrenoceptor–mediated effects, but it remains to be determined whether this development is triggered by epinephrine. The aim of this study was to characterize β -adrenoceptor–mediated relaxation and facilitation of norepinephrine release in the aorta of phenylethanolamine- N -methyltransferase–knockout (Pnmt-KO) mice. Catecholamines were quantified by reverse-phase high-performance liquid chromatography–electrochemical detection. Aortic rings were mounted in a myograph to determine concentration-response curves to selective β 1- or β 2-adrenoceptor agonists in the absence or presence of selective β 1- or β 2-adrenoceptor antagonists. Aortic rings were also preincubated with [3H]norepinephrine to measure tritium overflow elicited by electrical stimulation in the presence of increasing concentrations of nonselective β - or selective β 2-adrenoceptor agonists. β 2-Adrenoceptor protein density was evaluated by Western blotting and β 2-adrenoceptor localization by immunohistochemistry. Epinephrine is absent in Pnmt-KO mice. The potency and the maximal effect of the β 2-adrenoceptor agonist terbutaline were lower in Pnmt-KO than in wild-type (WT) mice. The selective β 2-adrenoceptor antagonist ICI 118,551 [(±)- erythro -( S *, S *)-1-[2,3-(dihydro-7-methyl-1 H -inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride] antagonized the relaxation caused by terbutaline in WT but not in Pnmt-KO mice. Isoproterenol and terbutaline induced concentration-dependent increases in tritium overflow in WT mice only. β 2-Adrenoceptor protein density was decreased in membrane aorta homogenates of Pnmt-KO mice, and this finding was supported by immunofluorescence confocal microscopy. In conclusion, epinephrine is crucial for β 2-adrenoceptor–mediated vasodilation and facilitation of norepinephrine release. In the absence of epinephrine, β 2-adrenoceptor protein density was decreased in aorta cell membranes, thus potentially hindering its functional activity.

Journal ArticleDOI
TL;DR: The clinician should consider using proximal IO infusion sites such as the sternum or humerus when administering advanced cardiac life support drugs to rapidly achieve maximal therapeutic concentrations.
Abstract: Objectives: Intraosseous (IO) access, enabling the rapid administration of epinephrine during cardiac arrest (CA), is crucial in promoting optimal postresuscitation outcomes in patients with poor vascular access. There is a question whether IO-administered epinephrine is equivalent to intravenously administered epinephrine during CA. Methods: The question guiding this evidence-based review was as follows: in adults suffering CA given epinephrine via the IO route, what is the resulting serum concentration of the drug compared to when administered intravenously? A search was conducted and the evidence appraised and leveled. Results: Four animal studies met the inclusion criteria. The sources showed no definitive evidence supporting equivalence between intravenous and IO epinephrine administered during CA. Intravenously administered epinephrine provides increased and faster appearing serum concentrations than IO-administered epinephrine. Evidence indicated epinephrine given via the sternal IO route ...

Journal ArticleDOI
14 Dec 2014
TL;DR: The adequate management of anaphylaxis requires rapid diagnosis, implementation of primary and secondary prevention measures, and immediate administration of subcutaneous epinephrine.
Abstract: Introduction: Anaphylaxis is a dramatic clinical emergency. It is a very severe, life-threatening generalized or systemic hypersensitivity reaction. Based on immunologic mechanism the anaphylaxis is divided in IgE, IgG, complement, or immune complexes-mediated vs non allergic anaphylaxis. There are a lot of etiologic factors of anaphylaxis, but the three principal immunologic triggers are drugs, insect stings, and foods. Regarding the clinical severity there are several proposed grading systems. The diagnosis of anaphylaxis is mainly clinical. Discussion: The anaphylaxis markers measured in clinical laboratories are total tryptase and histamine. There are some conditions that modulate the onset of anaphylaxis, acting as co- or augmentation factors, which significantly lower the allergen dose necessary for triggering anaphylaxis. The well-documented cofactors of anaphylaxis are physical exercise, alcohol consumption, some foods, co-administration of nonsteroidal anti-inflammatory drugs (NSAID), and concomitant infectious diseases. Development of anaphylaxis depends on the sensitization pattern, the proportion of the involved immunoglobulin classes, characteristics of the allergen, the proportion of the involved immunoglobulin classes, the avidity and affinity of immunoglobulins to bind an allergen, the route of allergen application, and, last but not least, the presence of cofactors of anaphylaxis. Conclusion: Anaphylaxis remains a continuous challenge for the diagnosis and treatment. The adequate management of anaphylaxis requires rapid diagnosis, implementation of primary and secondary prevention measures, and immediate administration of subcutaneous epinephrine.