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A university student with a background of atopy presented to her general practitioner (GP) 2 weeks following an episode of throat tightening and dizziness occurring after touching cashew nut to her lip. She took antihistamine medication immediately and went to sleep, fearing for her life. On waking, she felt astounded to be alive. Her symptoms resolved gradually over the following week. She waited 2 weeks for an appointment with her GP, who referred her to allergy clinic. Eight months later, she was still waiting for her clinic appointment, and was left fearing a future fatal reaction, having been provided with no interim treatment. Not all patients who have severe allergic reactions present to the emergency department. Living with the constant fear of anaphylaxis can be overwhelming for patients and their families, and it can negatively impact mental health. Therefore, we advise early allergy counselling and early EpiPen prescription.

Systemic administration of drugs that activate the noradrenergic or glucocorticoid system potentiates aversive memory consolidation and reconsolidation. The opposite happens with the stimulation of endocannabinoid signaling under certain conditions. An unbalance of these interacting neurotransmitters can lead to the formation and maintenance of traumatic memories, whose strength and specificity attributes are often maladaptive. Here we aimed to investigate whether originally low-intensity and precise contextual fear memories would turn similar to traumatic ones in rats systemically administered with adrenaline, corticosterone, and/or the cannabinoid type-1 receptor antagonist/inverse agonist AM251 during consolidation or reconsolidation. The high dose of each pharmacological agent evaluated significantly increased freezing times at test in the conditioning context one and nine days later when given alone post-acquisition or post-retrieval. Their respective low dose produced no relative changes when given separately, but co-treatment of adrenaline with corticosterone or AM251 and the three drugs combined, but not corticosterone with AM251, produced results equivalent to those mentioned initially. Neither the high nor the low dose of adrenaline, corticosterone, or AM251 altered freezing times at test in a novel, neutral context two and ten days later. In contrast, animals receiving the association of their low dose exhibited significantly higher freezing times than controls. Together, the results indicate that newly acquired and destabilized threat memory traces become more intense and generalized after a combined interference acting synergistically and mimicking that reported in patients presenting stress-related psychiatric conditions.

Thyroid hormones have an integral role in cardiac homeostasis, and hypothyroidism may be associated with impaired myocardial contractility, altered endothelial function, and blunted response to catecholamines. Herein, the case of a patient with undiagnosed severe hypothyroidism, who developed an acute myocardial infarction and cardiac arrest during sedation for bronchoscopy, is described. He required prolonged resuscitation, which included coronary catheterization and placement of an intra-aortic balloon pump. The resuscitation was noteworthy for blunted physiologic responses to large doses of epinephrine; in particular, persistent bradycardia without evidence of conduction abnormalities. On admission to the intensive care unit, he was hypothermic (31.4°C), bradycardic, and hypotensive. Laboratory investigations revealed profound hypothyroidism, and thyroid hormone replacement was initiated. Within hours of initiation of thyroid hormone replacement, the need for vasopressor support was reduced. He had a complete recovery and was discharged home neurologically intact. The authors of the present report believe that this favorable neurologic outcome could be attributed to efficient resuscitation, prompt coronary revascularization, and profound hypothermia likely related to a hypothyroidism-associated hypometabolic state.

A 26-year-old woman developed acute compartment syndrome (ACS) of her right hand secondary to reperfusion syndrome. She suffered an out-of-hospital cardiac arrest following a pregabalin overdose. Attending paramedics mistakenly gave intra-arterial epinephrine into her right brachial artery. On resolution of her brachial artery spasm, she developed a reperfusion injury to her right hand and subsequently ACS. A four-incision fasciotomy with carpal tunnel decompression was performed and was successful in reversing focal ischaemia and an irreversible functional deficit. This case demonstrates an unusual case of hand ACS secondary to temporary limb ischaemia and reperfusion syndrome following iatrogenic intra-arterial epinephrine administration. We also summarise the current available literature on ACS of the hand including the aetiology, treatment and use of an intracompartmental monitor.

Background: Cardiac autonomic neuropathy (CAN) is a complication of diabetes mellitus (DM) that is associated with increased mortality. Exercise-based assessment of autonomic function has identified diminished parasympathetic reactivation after exercise in type 2 DM. It is postulated herein, that this would be more prominent among those with type 1 DM. Methods: Sixteen subjects with type 1 DM (age 32.9 ± 10.1 years), 18 subjects with type 2 DM (55.4 ± 8.0 years) and 30 controls (44.0 ± 11.6 years) underwent exercise-based assessment of autonomic function. Two 16-min submaximal bicycle tests were performed followed by 45 min of recovery. On the 2 nd test, atropine (0.04 mg/kg) was administered near end-exercise so that all of the recovery occurred under parasympathetic blockade. Plasma epinephrine and norepinephrine levels were measured at rest, during exercise, and during recovery. Results: There were no differences in resting or end-exercise heart rates in the three groups. Parasympathetic effect on RR-intervals during recovery (p < 0.03) and heart rate recovery (p = 0.02) were blunted in type 2 DM. Type 1 DM had higher baseline epinephrine and norepinephrine levels (p < 0.03), and exhibited persistent sympathoexcitation during recovery. Conclusions: Despite a longer duration of DM in the study patients with type 1 versus type 2 DM, diminished parasympathetic reactivation was not noted in type 1 DM. Instead, elevation in resting plasma catecholamines was noted compared to type 2 DM and controls. The variable pathophysiology for exercise-induced autonomic abnormalities in type 1 versus type 2 DM may impact prognosis.

Background The role of platelets in the pathogenesis of venous thromboembolism (VTE) is receiving increasing attention; however, limited information is available on platelet function in the acute phase of the disease. Objective To characterize platelet function according to VTE phenotypes. Patients/Methods In total, 154 subjects (isolated pulmonary embolism [iPE], n = 28; isolated deep vein thrombosis [iDVT], n = 35; DVT+PE, n = 91) were included. In this study platelet function analyzer (PFA)-200, light transmission aggregometry (LTA), thrombin generation (TG) in presence (PRP) and absence (PFP) of platelets and platelet flow cytometry were investigated. LASSO regression was used to select clinical and platelet biomarkers that distinguish between VTE phenotypes. Results PFA-200 results did not differ between VTE phenotypes. LTA from DVT+PE subjects showed lowest maximum aggregation after epinephrine and adenosine diphosphate compared to iPE and iDVT. Lower % of PAC-1-positive platelets after in-vitro trigger were present in DVT+PE and iPE compared to iDVT. TG in PRP had lower peak height and velocity in DVT+PE and iPE against iDVT. The results of LASSO regression for the distinction between DVT+PE vs iDVT identified 18 variables (AUC =0.93) of which 72% were platelet biomarkers. For distinction between iPE and iDVT, 10 variables were selected (AUC = 0.96) of which 50% were platelet-related. Obesity was the only variable weakly discriminating between DVT+PE vs iPE (AUC = 0.66). Conclusion This explorative study suggests an important distinction between PE-related phenotypes and iDVT when considering clinical and platelet function data. Lower platelet-dependent TG along with reduced platelet reactivity suggest higher platelet degranulation in PE-dependent phenotypes compared to iDVT.

Anaphylaxis-related emergency department (ED) visits and hospitalizations are increasing. Triggers for anaphylaxis include food, medications, and stinging insects. Idiopathic anaphylaxis accounts for 30% to 60% of cases of anaphylaxis in adults and up to 10% of cases in children with novel allergens such as galactose-α-1,3 galactose reclassifying these cases. Recent practice guidelines have recommended against the routine use of systemic corticosteroids and antihistamines for the prevention of biphasic reactions and recommend an extended observation, up to 6 hours, for those with risk factors for biphasic anaphylaxis and those with lack of access to epinephrine and to emergency medical services.

Epinephrine is a lifesaving medication to treat systemic allergic reactions including anaphylaxis. Epinephrine autoinjectors (EAIs) are expensive, not available everywhere in the world, and shortages can limit their access. Epinephrine prefilled syringes and epinephrine kits are lower-cost alternatives to EAIs. Advantages, disadvantages, and costs of available products are discussed and the socioeconomic factors impacting access to EAIs described. EAIs designed for infants also are discussed.

Food allergies are a common and serious cause of illness, accounting for an increasing number of emergency department visits annually. Although definite diagnosis lays outside of an emergency department visit, the clinical management of the most serious food allergies highlights emergency care. The staple of acute care remains epinephrine in association with antihistamines and steroids. The greatest threat remains undertreatment for this group of disorders and underutilization of epinephrine. Those who have been treated for a food allergy need a follow-up allergist evaluation, guidance of food avoidance, and avoidance of foods with cross-sensitivities as well as ready access to epinephrine.

There are many definitions of anaphylaxis in the medical literature. The authors propose a modified definition of anaphylaxis to be used for clinical decision making that promotes the early utilization of intramuscular epinephrine. Anaphylaxis can be a result of an allergic or nonallergic mechanism. In general, allergic reactions are more severe; however, any type of anaphylaxis can result in death and improve with IM epinephrine. The World Allergy Organization's Grading Criteria for allergic systemic reactions are adapted as a guide to identify manifestations that may progress to anaphylaxis. The intent is to promote and encourage the use of IM epinephrine in the health care setting before the progression of manifestations and the onset of life-threatening respiratory or cardiovascular dysfunction generally recognized as meeting the definition of anaphylaxis.

After treating the acute anaphylactic reaction, the clinician's next task is to prevent a recurrence. The patient should be observed in the ED. How long this observation period should last depends on their clinical course, risk factors, and social support. All patients should be discharged with a prescription for 2 epinephrine autoinjectors and counseled on appropriate use. The patient should also receive education on the signs and symptoms of anaphylaxis and avoiding triggers. The patient should follow-up with an allergy specialist who can confirm triggers and provide immunotherapy as indicated.

Perioperative anaphylaxis is relatively rare but can be life-threatening. The incidence in China is unknown and may differ from other global geographic regions. This study was therefore designed to understand the incidence of perioperative anaphylaxis in China.We enrolled 112 tertiary care hospitals from seven distinct geographic areas in mainland China. We collected information about Ring and Messmer III and IV reactions from September 2018 to August 2019. A collaborative educational learning network was used to reduce diagnostic errors. Information about patient characteristics, clinical features, treatment, and clinical outcomes were recorded and analysed.A total of 447 cases of 5 078 118 surgical procedures met inclusion criteria. The incidence of suspected perioperative anaphylaxis throughout China was one in 11 360 anaesthetics (95% confidence interval [CI], with a range of 1:12 521 to 1:10 397). The incidence in South China was higher (one in 6050; 95% CI, from 1:8013 to 1:4859) than in Northeast China (one in 19 262; 95% CI, from 1:33 088 to 1:13 585) (P0.01) with an increasing trend from the north to the south. The most common clinical manifestations were hypotension (91.1%) and tachycardia (65.3%). The majority of patients (83.4%) were given epinephrine. A total of 27 patients (6.0%) required cardiopulmonary resuscitation. Ultimately, nine patients died (2.0%).This nationwide survey showed an incidence of perioperative anaphylaxis of one in 11 360, but this varied significantly by region. The underlying reason for this pattern remains unknown and could be attributable to environmental or genetic influences, which requires further investigation.ChiCTR1900025956.

Although there is a general perception that the prevalence of food allergy is increasing, data supporting this are limited. Food is the least common cause of fatal anaphylaxis, and fortunately, it is a very rare event; however, it is also unpredictable. There is widespread consensus that severe reactions cannot be predicted in a clinically meaningful way. Certain food triggers are more frequently associated with fatal anaphylaxis than others. In observational studies, peanut and tree nuts account for at least 30% to 50% of fatalities, with seafood and cow's milk also associated with fatal reactions. Fatal food-induced anaphylaxis is most likely to occur during adolescence and young adulthood, although the reasons for this are unclear. International guidelines agree that intramuscular (IM) epinephrine is the treatment of choice for managing food-triggered anaphylaxis and has a good safety profile when given by the IM route. However, fatalities still occur despite the timely administration of epinephrine. Food-allergic individuals must navigate a world that requires daily vigilance for allergens and preparedness for allergic reactions. Although the actual risk of fatal reactions is minimal, it is not zero, and severe reactions are unpredictable. Clinicians need to help patients better understand the very low but real risk of fatal reaction and enable them to lead as normal a life as possible through appropriate education, safety netting, and risk reduction.

Hypomagnesemia is defined as serum [Mg2+] < 1.7 mg/dL. The prevalence of hypomagnesemia in outpatient and hospitalized patient population is 6–12 %. The incidence of hypomagnesemia is approximately 65 %. The causes of hypomagnesemia fall into four major categories: (1) decreased intake of Mg2+; (2) decreased intestinal absorption; (3) increased urinary losses; and (4) drugs. In addition to these causes, transcellular transport of Mg2+ into the cell is caused by infusion of glucose or epinephrine.

Anaphylaxis is a medical emergency with adrenaline acknowledged as the first line therapy. It is therefore important that patients have access to self-injectable adrenaline in the community. Manufacturers have been requested by European Medicine Regulators to generate pharmacokinetic data for these autoinjector devices. For the first time, these data provide an insight into how individual devices work in different populations, and how they compare. We undertook a thorough literature search and also accessed grey literature, using searches of medicine regulators' websites and freedom of information requests. The data demonstrate that it takes at least 5-10 minutes to achieve early peak plasma concentration for most devices. The specific autoinjector device seems to be the most important determinant of pharmacokinetics, with different devices giving rise to different plasma adrenaline profiles. Needle length does not seem to be the most important factor; rather, the force and speed of injection (which varies from one device to another) is likely to be of greater importance. In general, peak plasma adrenaline concentration is lower and time-to-peak concentration longer with increased skin-to-muscle depth. However, it is difficult to draw conclusions with the current available data, due to a lack of head-to-head comparisons, small numbers of study participants, and the failure to acknowledge the biphasic nature of intramuscular adrenaline absorption for analysis purposes.

The objective of this study is to develop an evidence-based nursing practice protocol to cope with anaphylaxis by identifying the effect of early administration of epinephrine on the recovery of patients when anaphylaxis occurs due to computed tomography (CT) contrast agents, and to evaluate its feasibility. Anaphylaxis caused by CT contrast agents is a life-threatening systemic hypersensitivity reaction compared to normal allergic reactions, requiring immediate administration of epinephrine and other emergency drugs; however, no practical guidelines have been established for such emergency management, requiring the development of evidence-based nursing practice protocols. The study design is a methodological and cross-sectional study that aims to develop an evidence-based nursing practice protocol. An evidence-based nursing practice protocol for anaphylaxis management generated by contrast agents was developed in accordance with the 3-step (12 more specific steps) development of clinical practice guideline based on the literature of the final 12 selected (including 2 guidelines). It was applied to practice after implementing the training of the medical staff on the final protocol developed, and evaluated the effectiveness of anaphylaxis management for 6 months before and after the application of the protocol. Based on the analysis of the evidence, we make six recommendations for managing anaphylaxis caused by contrast agents based on early administration of epinephrine and apply the protocol to clinical practice. After protocol application, awareness of anaphylaxis and onset time of epinephrine administration was accelerated, but significant differences were not confirmed. In the case of anaphylaxis due to CT contrast agents, evidence-based coping protocols were created. The developed protocol should be continued for use in practice, with continued assessment of its effectiveness.

Parturition is the physiological process of newborn birth; more and more evidences show that parturition is closely related to the occurrence and resolution of inflammation. However, the inflammatory media and the mechanism are not very clear during parturition. Here, we investigate the inflammatory event during human parturition and in mouse model. We found that the pro-inflammatory cytokines (IL-6, IL-8, and IL-1β) and cells (neutrophil and macrophage) are decreased in pregnant women in labor and in mouse labor model. Mechanistically, increased stress stimulates the high-level adrenaline production in labor. Then, adrenaline upregulates the expression of 12/15-LOX (lipoxygenase) to produce more lipoxin A4 (LXA4), which is an inflammation inhibitor. Thus, LXA4 promotes the elimination of inflammation during labor to protect the body from excessive inflammatory damages. In addition, using BOC-2, the inhibitor of LXA4 receptor could reboot the pro-inflammatory cytokines. Our study indicates that LXA4 is induced by adrenaline in labor and appropriate interference of this pathway may be a potential strategy to regulate the inflammatory process in parturition.

Psychosocial stress is a key contributing factor to the pathogenesis of hypertension and cardiovascular disease. We examined the association of urinary stress hormone levels with incident hypertension and cardiovascular events. This prospective cohort study included 412 adults (age 48–87 years) free of hypertension from the Multi-Ethnic Study of Atherosclerosis with measurements of urinary stress hormones (norepinephrine, epinephrine, dopamine, and cortisol). Multivariable Cox proportional hazard models were used to estimate the adjusted hazard ratio (aHR) of incident hypertension and cardiovascular events according to urinary stress hormone levels. The average age (SD) was 61.2 (9.1) years, and 50% were female. Over a median follow-up of 6.5 years, there was an increased risk of incident hypertension per doubling of norepinephrine (aHR, 1.31 [95% CI, 1.06–1.61]), epinephrine (aHR, 1.21 [95% CI, 1.03–1.41]), dopamine (aHR, 1.28 [95% CI, 1.00–1.64]), and cortisol (aHR, 1.23 [95% CI, 1.04–1.44]). The associations were generally stronger among participants P -for-interaction, 0.04) and cortisol ( P -for-interaction, 0.04). Over a median follow-up of 11.2 years, there was an increased risk of incident cardiovascular events per doubling of cortisol (aHR, 1.90 [95% CI, 1.16–3.09]), but not for catecholamines. In this multiethnic population study, higher urinary stress hormone levels were associated with an increased risk of incident hypertension. Urinary cortisol levels were also associated with an increased risk of incident cardiovascular events. Our findings highlight a potentially important role of stress hormones in the prevention and treatment of hypertension and cardiovascular diseases.

BACKGROUND The effects of adrenaline on cerebral blood vessels during cardiopulmonary resuscitation (CPR) are not well understood. We developed an extracorporeal CPR model that maintains constant low systemic blood flow while allowing adrenaline-associated effects on cerebral vasculature to be assessed at different mean arterial pressure (MAP) levels independently of the effects on systemic blood flow. METHODS After eight minutes of cardiac arrest, low-flow extracorporeal life support (ECLS) (30 ml/kg/min) was started in fourteen pigs. After ten minutes, continuous adrenaline administration was started to achieve MAP values of 40 (n = 7) or 60 mmHg (n = 7). Measurements included intracranial pressure (ICP), cerebral perfusion pressure (CePP), laser-Doppler-derived regional cerebral blood flow (CBF), cerebral regional oxygen saturation (rSO2), brain tissue oxygen tension (PbtO2) and extracellular cerebral metabolites assessed by cerebral microdialysis. RESULTS During ECLS without adrenaline, regional CBF increased by only 5% (25th to 75th percentile: -3 to 14; p = 0.2642) and PbtO2 by 6% (0-15; p = 0.0073) despite a significant increase in MAP to 28 mmHg (25-30; p

In this study, we examine the impact of a trauma-based resuscitation protocol on survival outcomes following emergency medical services (EMS) witnessed traumatic out-of-hospital cardiac arrest (OHCA).We included EMS-witnessed OHCAs arising from trauma and occurring between 2008 and 2019. In December 2016, a new resuscitation protocol for traumatic OHCA was introduced prioritising the treatment of potentially reversible causes before conventional cardiopulmonary resuscitation. The effect of the new protocol on survival outcomes was assessed using adjusted multivariable logistic regression models.Paramedics attempted resuscitation on 490 patients, with 341 (69.6%) and 149 (30.4%) occurring during the control and intervention periods, respectively. A reduction in the proportion of cases receiving cardiopulmonary resuscitation and epinephrine administration were found in the intervention period compared to the control period, whereas trauma-based interventions increased significantly, including blood administration (pre-arrest: 17.9% vs 3.7%; intra-arrest: 24.1% vs 2.7%), splinting (pre-arrest: 38.6% vs 17.1%; intra-arrest: 20.7% vs 5.2%), and finger thoracostomy (pre-arrest: 13.1% vs 0.6%; intra-arrest: 22.8% vs 0.9%), respectively, with p-values 0.001 for all comparisons. After adjustment, the trauma-based resuscitation protocol was not associated with an improvement in survival to hospital discharge (AOR 1.29, 95% CI: 0.51-3.23), event survival (AOR 0.72, 95% CI: 0.41-1.28) or prehospital return of spontaneous circulation (AOR 0.63, 95% CI: 0.39-1.03).In our region, the introduction of a trauma-based resuscitation protocol led to an increase in the delivery of almost all trauma interventions; however, this did not translate into better survival outcomes following EMS-witnessed traumatic OHCA.

Background/Aims: Peptic ulcer bleeding is the most common cause of upper gastrointestinal tract bleeding. Platelet-rich plasma (PRP) enhances tissue repair, and is therefore used in various medical treatments. A combination of mechanical or electrothermal hemostasis has been recommended for upper gastrointestinal tract bleeding treatment. This study evaluated the additive efficacy of PRP in bleeding peptic ulcer hemostasis and recovery.Methods: Eighty patients with peptic ulcer bleeding were initially treated by hemoclipping, and were randomly chosen for either additional PRP (n=40) or additional epinephrine (n=40) injections. Both groups were compared with regard to achieving hemostasis and the frequency of complications.Results: Hemostasis was immediately achieved in both groups. Two patients (5%) in the PRP group and 8 (20%) patients in the epinephrine group experienced rebleeding after 15.9±2.8 and 12.3±3.7 days, respectively. They were managed by PRP injection in addition to proton pump inhibitor infusion. Hemoglobin was substantially increased in the PRP-treated group with full recovery occurring in 60.5% compared to 31.3% of patients in the epinephrine group (p=0.001). There was no recurrent bleeding in the PRP group, but 4/32 (12.5%) patients in the epinephrine group exhibited rebleeding.Conclusions: PRP showed additional benefit in reducing peptic ulcer bleeding with no reported significant complications. Clinical trial (NCT03733171).

Publisher Copyright: © 2021 The Authors Objective: Airway management to ensure sufficient gas exchange is of major importance in emergency care. Prehospital endotracheal intubation (ETI) by paramedics is a widely debated method to ensure a patent airway. ETI is performed with procedural sedation in comatose patients because of the regulation. The use of medications increases the rate of successful airway management compared with nonmedication ETI and may also improve outcomes in patients with traumatic brain injury. In the absence of an operative emergency physician and with long distances, paramedic-induced airway management may increase the survival of patients in selected scenarios. A paramedic-staffed helicopter emergency medical system in Northern Finland operates in a rural area without an emergency physician and paralytic medications and treats critically ill patients using basic or advanced life support ground units. The aim of this study was to evaluate the success rates of ETI performed by a small, appropriately trained, and experienced group of 8 nurse paramedics in an out-of-hospital setting. Methods: The inclusion criterion for the study was an attempted intubation in patients with medical or traumatic indication for airway management by nurse paramedic. Results: Fifty-one patients were treated with ETI. The first-pass success rate was 72.5%, the second-pass success rate was 94.1%, and the overall success rate was 100% within 4 attempts. The median on-scene time was 54 minutes, and there were no signs of aspiration during laryngoscopy or after successful ETI. The primary mortality rate was 11.7%. Conclusion: The use of a rigid standard operating procedure for paramedic rapid sequence induction, paralytics, a video laryngoscope, and a gum elastic bougie might positively affect the ETI first-pass success rate. A follow-up study after these future modifications is needed. This small study suggests that intubation might be 1 option for airway management by an experienced nonanesthesiologist in Lapland.

Arthroscopy has become increasingly relevant to various subspecialties within the orthopaedic surgery. From a patient safety standpoint and surgical efficiency standpoint, it is critical to know the fundamental concepts of fluid management such as those related to the fluid, pressure, and flow. A satisfactory field of view during arthroscopy can be achieved with the use of gravity-dependent or automated fluid management systems. Fluid management parameters and their physiological impact on the patient should be continuously monitored to avoid morbidity or delayed recovery. Local and systemic complications can occur from careless use of techniques that improve visualization such as tourniquet, epinephrine-diluted irrigation, and controlled hypotensive anesthesia. The purpose of this article is to review the fundamental concepts of fluid management in arthroscopy and the techniques to safely improve arthroscopic visualization.

La anafilaxia es una causa poco frecuente de síndrome coronario agudo por vasoespasmo con o sin la presencia de enfermedad coronaria subyacente. Presentamos el caso de un síndrome de Kounis en un paciente masculino sin factores de riesgo conocidos para enfermedad coronaria quien presentó un síndrome coronario agudo con elevación de ST que requirió manejo con adrenalina, soporte vital básico e ingreso a Unidad de Cuidados Intensivos; con arteriografía coronaria sin evidencia de enfermedad subyacente.

Objetivo: Caracterizar clínicamente los eventos de anafilaxia en un hospital pediátrico de tercer nivel. Métodos: Se revisaron 1148 expedientes clínicos. Finalmente, se analizó la información correspondiente a 35 episodios de anafilaxia en 20 pacientes; tres de ellos con múltiples episodios de anafilaxia. Resultados: La edad mediana de los episodios de anafilaxia fue de 11 años (rango intercuartilar 10 años, Q1 = 5, Q3 = 15), con predomino en adolescentes de 12 a 17 años y del sexo femenino. Las manifestaciones clínicas más frecuentes fueron las cutáneas (86 %), seguidas de las respiratorias (83 %), las cardiovasculares (74 %) y las gastrointestinales (46 %). En tres casos se documentó paro cardiorrespiratorio, pero no hubo casos de mortalidad asociada a anafilaxia. Los principales desencadenantes fueron alimentos (34 %), medicamentos (29 %), inmunoterapia para alérgenos (14 %) y látex (11 %). En los pacientes con anafilaxia perioperatoria el comportamiento clínico fue grave. La adrenalina se utilizó en 27 de los 35 episodios (77 %), en 11 de ellos fue el tratamiento de primera elección. Los corticosteroides sistémicos fueron los medicamentos más frecuentemente utilizados, seguidos de la adrenalina y los antihistamínicos. Conclusiones: El uso de adrenalina, pilar del tratamiento de anafilaxia, es subóptimo; con uso preferente de medicamentos de segunda línea como los corticosteroides. Se requieren protocolos para diagnóstico y tratamiento de anafilaxia, aunado a una educación continua del personal de salud.

The incidence of anaphylaxis is increasing in children. Children suffering from anaphylaxis represent a complex and ambiguous group of patients. The factors that cause difficulties in diagnosing anaphylaxis in children are as follows: a wide range of triggers, unpredictability of the nature, severity of clinical symptoms of systemic reactions, and their age-dependent interpretation. The first anaphylactic reaction always stuns parents and medical staff, which leads to a subjective description of the anamnesis and a delay in making a diagnosis and prescribing the correct treatment. For these patients, problems such as the lack of available diagnostic tests for verifying the diagnosis of anaphylaxis, restriction of standard doses of epinephrine autoinjectors, lack of predictors of the occurrence, and severity of systemic allergic reactions continue to be relevant. The article focused on the most urgent difficulties and features of managing patients with anaphylaxis in pediatric practice and discussed possible prospects and ways to solve them.

OBJECTIVE The renin-angiotensin-aldosterone system (RAAS) plays a relevant role in regulating blood pressure and thus maintaining cardiovascular homeostasis. While it was recently shown that RAAS parameters are responsive to acute psychosocial stress, the psychobiological determinants of the acute stress-induced RAAS activation have not yet been investigated so far. In a randomized placebo-controlled design, we investigated potential psychological and physiological determinants of the RAAS response and underlying mechanisms. METHODS 57 young healthy male participants underwent either an acute standardized psychosocial stress test or a non-stress placebo task. We measured aldosterone in plasma and saliva, as well as renin, and the stress-reactive endocrine measures adrenocorticotropic hormone (ACTH), epinephrine, and norepinephrine in plasma at rest, immediately after the task and several times up to 3 h thereafter. Moreover, we assessed stress-reactive psychological (anticipatory cognitive stress appraisal, mood, physical discomfort) and basal demographic-physiological measures (age, BMI, blood pressure). RESULTS Acute psychosocial stress elicited changes in all assessed endocrine (p's ≤ .028, ηp2's ≥ .07) and stress-reactive psychological measures (p's ≤ .003, ηp2's ≥ .15). The basal parameter BMI, the stress-reactive endocrine parameters ACTH and norepinephrine, and the psychological parameter anticipatory stress appraisal were identified as determinants of higher RAAS parameter reactivity to acute psychosocial stress. The association between anticipatory cognitive stress appraisal and plasma RAAS measures was fully mediated by ACTH increases (p's ≤ .044, ηp2's ≥ .05). CONCLUSIONS Cognitive stress appraisal processes seem to modulate RAAS stress reactivity. This points to potential clinical implications for psycho-educative therapeutical interventions targeting stress appraisal processes in order to reduce endocrine stress reactivity.

Background: No-reflow is considered a major percutaneous coronary intervention complication, especially in primary PCI. A variety of medications have been studied for no-reflow treatment, including intracoronary nitrates, verapamil, adenosine, glycoprotein IIb/IIIa inhibitors, and epinephrine. Glycoprotein IIb/IIIa inhibitors and epinephrine are the two most promising agents for the treatment of no-reflow. Aim of work: evaluating epinephrine and glycoprotein IIb/IIIa inhibitors efficacy in treating no-reflow through local distal intracoronary injection in comparison to traditional intracoronary administration in the guiding catheter. Subjects and methods: 30 patients undergoing PCI complicated by no-reflow phenomenon. Patients were randomized to either group I where they were treated by local distal intracoronary injection of GP IIb/IIIa inhibitor and epinephrine or to group II where they received the same medications via the traditional intracoronary injection. Primary outcomes were TIMI flow, corrected TIMI frame count and TMPG, and major adverse cardiac events within 48 hours was the secondary outcome. Results: Group I had significantly superior angiographic outcomes than group II. As regards TIMI II-III flow, 86.7% of patients achieved it in versus 53.3% in group II, CTFC was 8.2versus 9.9, and in group I, 80% of patients achieved TMPG II-III, compared to 46.7 % in group II. MACE was insignificantly different between both groups. Diabetes mellitus was found to be the only predictor to be negatively associated with TIMI flow. Conclusion: Distal coronary artery local injection of a combination of GP IIb/IIIa inhibitors and epinephrine achieved superior angiographic outcomes in the treatment of refractory no-reflow in comparison with traditional intracoronary administration of the same medications.

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Introduction Overall survival of patients with out-of-hospital cardiac arrest (OHCA) remains low, even in those with return of spontaneous circulation (ROSC). In addition to usual prognostic characteristics, patients’ medical history may also influence their outcome. This study aimed to investigate the role of pre-arrest comorbidities on hospital survival, neurological outcome and mode of death in OHCA patients with successful ROSC. Methods From Jan 2012 to Sep 2017, all consecutive non-traumatic OHCA adults, admitted with a stable ROSC were included. Utstein characteristics, circumstances of arrest and interventions were prospectively recorded. Prior comorbidities were measured using the Charlson Comorbidity Index (CCI), and the population was divided into 3 groups (CCI 0, CCI 1–3 and CCI ≥ 4). The association of CCI with early and long-term mortality was assessed using logistic regression and association with withdrawal-of-life sustaining treatments (WLST) or another cause of death using multinomial regression. Results During the study period, 777 patients were analyzed and 483 (62%) died before hospital discharge, with death rate of 49%, 60% and 70% in CCI 0, CCI 1–3 and CCI ≥ 4 respectively. After adjustment, an increase CCI was significantly associated with in-hospital mortality (OR = 2.47 [1.35–4.52], p = 0.001 for CCI 1–3; OR = 2.82 [1.49–5.33], p = 0.003 for CCI ≥ 4; ref = CCI 0). Other independent predictors were non-shockable rhythm (OR = 3.23 [2.08–5]), lack of bystander CPR (OR = 1.96 [1.22–3.13]), epinephrine dose ≥ 2 mg (OR = 5.56 [3.70–8.33]), CA to CPR ≥ 5 min (OR = 1.96 [1.28–3.03]) and CPR to ROSC ≥ 20 min (OR = 2.13 [1.39–3.23]). Using multinomial regression, an increase in CCI was associated with all modes of in-hospital death, particularly with WLST-related death (RRadj = 2.48 [1.26–4.90], p = 0.01 for CCI = 1–3 and 3.75 [1.85−8.7.58], p Conclusion Alteration of chronic health status, as assessed by an elevated CCI, was associated with a higher mortality and a worse neurological outcome in OHCA patients. Presence and burden of comorbidities should be considered in the evaluation of the prognosis in patients admitted in hospital after cardiac arrest.

Introduction Early recognition of an anaphylaxis event is crucial for instituting lifesaving management. We sought to explore knowledge and practice towards anaphylaxis in a sample of physicians from ten Egyptian governorates. Methods An eighteen question-based questionnaire was developed by expert allergists to evaluate the knowledge and practice towards anaphylaxis, based on the World Allergy Organization guidelines for the assessment and management of anaphylaxis. The questionnaires were distributed, and the answered forms collected via emails, and data were tabulated, and analysed. Results In this cross-sectional study, a total of 242 physicians completed the survey (183 (75.6%) paediatricians, 32 (13.2%) internists, 22 (9.1%) intensivists and five (2.1%) anaesthetists). Only 91 participants (37.6%) identified all the four proposed anaphylaxis clinical scenarios while 70, 45 and 36 identified three, two and one scenario, respectively. Loss of consciousness and abdominal symptoms were not recognised as possible presentations of anaphylaxis by 64.5% and 80.2% of the participants, respectively. Epinephrine was considered the first line treatment by 98 (40.5%), corticosteroids by 77 (31.8%) and antihistamines by 25 (10.3%). 75 (31%) responders identified the right dose of epinephrine while 119 (49.2%) identified the proper route. Concerning practice, 83 physicians (39.2%) used epinephrine for all cases of anaphylaxis, 88 (41.5%) used it for refractory cases only whereas 41 (19.3%) did not use epinephrine at all. Discussion Our survey shows that the knowledge of Egyptian physicians and their practice towards anaphylaxis are still inadequate. The current situation reinforces the need to disseminate and encourage the adoption of the international guidelines for anaphylaxis diagnosis and treatment.

The parameters of coupled respiration and transport of calcium ions in mitochondria isolated from the heart of rats were studied in two modes of exposure to epinephrine for modelling myocardial damage. In 24 h after injection of 1.5 mg/kg epinephrine to rats, we observed a decrease in the efficiency of oxidative phosphorylation in heart mitochondria in the presence of both NADH- and FADH-dependent respiratory substrates. Increasing the epinephrine dose and exposure (2 mg/kg, 72 h) led to a more pronounced decrease in the ADP/O coefficient when succinate was used as a substrate, which indicated a predominant decrease in the activity of complex II of the respiratory chain. The injection of epinephrine in the two modes resulted in a decrease in the rate of calcium entry in rat heart mitochondria, but had no effect on mitochondrial calcium retention capacity, which reflects the resistance of the organelles to the induction of the Са2+-dependent pore. These findings suggest that both cardiomyopathy models in rats can be used to study the effectiveness of pharmacological therapy using mitochondria-targeted agents.

Anaphylaxis is a life-threatening systemic allergic reaction presenting various clinical manifestations. Its prevalence has increased in almost all age groups and both sexes. Food, venom, and drugs are major causes in both children and adults; a higher prevalence of food-induced anaphylaxis is noted in children, while a higher prevalence of drug-induced anaphylaxis is noted in adults. The pathogenic mechanism is mediated by immunologic and nonimmunologic mechanisms, where mast cells and basophils are key cells that release mediators. A diagnosis of anaphylaxis is mainly based on clinical symptoms and physical findings; however, an increased serum tryptase level is a useful biomarker. Epinephrine is the first-line drug to treat acute symptoms, and an epinephrine auto-injector should be prescribed for each patient. Antihistamines and systemic corticosteroids are used to relieve symptoms. This review updates current issues in the management of anaphylaxis as well as the new guidelines for proper diagnosis and treatment.

BackgroundInternational asthma guidelines recommend against epinephrine (adrenaline) administration in acute asthma unless associated with anaphylaxis or angio-oedema. However, administration of intramuscular epinephrine in addition to nebulised selective β2-agonist is recommended for acute severe or life-threatening asthma in many prehospital guidelines. We conducted a systematic review to determine the efficacy of epinephrine in comparison to selective β2-agonist in acute asthma.MethodsWe included peer-reviewed publications of randomised controlled trials (RCTs) that enrolled children or adults in any healthcare setting and compared epinephrine by any route to selective β2-agonist by any route for an acute asthma exacerbation. The primary outcome was treatment failure, including hospitalisation, need for intubation or death.ResultsThirty-eight of 1140 studies were included. Overall quality of evidence was low. Seventeen studies contributed data on 1299 participants to the meta-analysis. There was significant statistical heterogeneity, I2=56%. The pooled Peto’s OR for treatment failure with epinephrine versus selective β2-agonist was 0.99 (0.75 to 1.32), p=0.95. There was strong evidence that recruitment age group was associated with different estimates of the odds of treatment failure; with studies recruiting adults-only having lower odds of treatment failure with epinephrine. It was not possible to determine whether epinephrine in addition to selective β2-agonist improved outcomes.ConclusionThe low-quality evidence available suggests that epinephrine and selective β2-agonists have similar efficacy in acute asthma. There is a need for high-quality double-blind RCTs to determine whether addition of intramuscular epinephrine to inhaled or nebulised selective β2-agonist improves outcome.PROSPERO registration numberCRD42017079472.

Мета: дати характеристику стану здоров’я дітей із зони антитерористичної операції (АТО) на сході України з кардіоревматологічною патологією і вивчити у них показники стрес-регулюючих систем. Матеріали та методи. Проведено клініко-інструментальне обстеження 126 дітей віком 8–18 років, із них 92 дитини із зони антитерористичної операції і 34 дитини-переселенця з Донецької та Луганської областей. Групу порівняння становили 509 дітей того ж віку з Харківської області і міста Харкова. Інтенсивність стрес-реалізуючих систем визначали за рівнем кортизолу, ТБК-активних продуктів і дієнових кон’югатів у сироватці крові, адреналіну і норадреналіну в добовій сечі. Стан стрес-лімітуючих систем оцінювали за вмістом серотоніну, відновленого глутатіону, активності глутатіонпероксидази і супероксиддисмутази (СОД) у крові і мелатоніну в сечі. Результати. У структурі соматичної патології у дітей і підлітків із зони військових дій на сході України кардіоревматологічні захворювання посідають друге місце, перше місце належить хворобам органів травлення. У 34,1 % дітей, які вперше потрапили в клініку інституту, погіршення стану здоров’я настало на тлі психоемоційного напруження і відсутності умов для лікування за основним місцем проживання. У структурі скарг пацієнтів переважали астеноневротичні, які вірогідно частіше зустрічалися у дітей першої групи. Також найчастіше діагностували різні психосоматичні розлади, захворювання органів травлення і ендокринопатії. Вивчення стрес-регулюючих систем у дітей із зони АТО виявило деякі відмінності в показниках з урахуванням нозологічної приналежності. Так, у хворих з серцево-судинною патологією відзначалася активація стрес-реалізуючих систем, а у дітей з ревматичними захворюваннями — напруга стрес-лімітуючих систем. Виявлені зміни рівня мелатоніну та активності СОД у пацієнтів із захворюваннями органів кровообігу із зони АТО свідчать про дисбаланс антиоксидантів ферментної і неферментної природи, що може призвести до виникнення оксидативного стресу як однієї зі складових посттравматичного стресового розладу. Таким чином, отримані дані необхідно враховувати при складанні індивідуальних програм відновного лікування дітям і підліткам з кардіоревматологічною патологією із зони військових дій з урахуванням супутньої патології. Висновки. У дітей із зони військових дій виявлено дисбаланс компонентів антиоксидантного стресу, відповідальних за стресостійкість організму до факторів пошкодження. Встановлено активацію стрес-реалізуючих систем при хворобах органів кровообігу і напругу стрес-лімітуючих систем при ревматичних захворюваннях., Цель: дать характеристику состояния здоровья детей из зоны антитеррористической операции (АТО) на востоке Украины с кардиоревматологической патологией и изучить у них показатели стресс-регулирующих систем. Материалы и методы. Проведено клинико-инструментальное обследование 126 детей в возрасте 8–18 лет, из них 92 ребенка из зоны антитеррористической операции и 34 ребенка-переселенца из Донецкой и Луганской областей. Группу сравнения составили 509 детей того же возраста из Харьковской области и города Харькова. Интенсивность стресс-реализующих систем определяли по уровню кортизола, ТБК-активных продуктов и диеновых конъюгатов в сыворотке крови, адреналина и норадреналина в суточной моче. Состояние стресс-лимитирующих систем оценивали по содержанию серотонина, восстановленного глутатиона, активности глутатионпероксидазы и супер­оксиддисмутазы (СОД) в крови и мелатонина в суточной моче. Результаты. В структуре соматической патологии детей и подростков из зоны военных действий на востоке Украины кардиоревматологические заболевания занимают второе место, первое место принадлежит болезням органов пищеварения. У 34,1 % детей, впервые поступивших в клинику института, ухудшение состояния здоровья наступило на фоне психоэмоционального напряжения и отсутствия условий для лечения по основному месту проживания. В структуре жалоб пациентов преобладали астеноневротические, которые достоверно чаще встречались у детей первой группы. Также чаще всего диагностировались различные психосоматические расстройства, заболевания органов пищеварения и эндокринопатии. Изучение стресс-регулирующих систем у детей из зоны АТО выявило некоторые различия в показателях с учетом нозологической принадлежности. Так, у больных с сердечно-сосудистой патологией отмечалась активация стресс-реализующих систем, а у детей с ревматическими заболеваниями — напряжение стресс-лимитирующих систем. Выявленные изменения уровня мелатонина и активности СОД у пациентов с заболеваниями органов кровообращения из зоны АТО свидетельствуют о дисбалансе антиоксидантов ферментной и неферментной природы, что может привести к возникновению оксидативного стресса как одного из составляющих посттравматического стрессового расстройства. Таким образом, полученные данные необходимо учитывать при составлении индивидуальных программ восстановительного лечения детям и подросткам с кардиоревматологической патологией из зоны военных действий с учетом сопутствующей патологии. Выводы. У детей из зоны военных действий выявлен дисбаланс компонентов антиоксидантного стресса, ответственных за стрессоустойчивость организма к повреждающим факторам. Установлена активация стресс-реализующих систем при болезнях органов кровообращения и напряжение стресс-лимитирующих систем при ревматических заболеваниях., Background. To characterize the health status of children from the antiterrorist operation zone in the east of Ukraine with cardiorheumatologic pathology and to study the indicators of stress-regulating systems was the purpose of our work. Materials and methods. A clinical and instrumental exa­mination was performed in 126 children aged 8–18 years, 92 of them from the anti-terrorist operation zone and 34 immigrant children from the Donetsk and Luhansk regions. The comparison group consisted of 509 children of the same age from the Kharkiv region and Kharkiv. The intensity of stress-realizing systems was determined by the level of cortisol, thiobarbituric acid-active products and diene conjugates in the blood serum, epinephrine and norepinephrine in daily urine. The state of stress-limiting systems was assessed by the content of serotonin, reduced glutathione, activity of glutathione pe­roxidase and superoxide dismutase in the blood and melatonin in daily urine. Results. In the structure of somatic pathology of children and adolescents from zone of military operations in the east of Ukraine, cardiorheumatologic diseases rank se­cond, the first place belongs to diseases of the digestive system. In 34.1 % of children admitted to the institute for the first time, the deterioration of health occurred against the background of psychoemotional stress and lack of conditions for treatment in the main place of residence. In the structure of patients’ complaints, astheno-neurotic ones prevailed, which was significantly more frequent in children of the first group. Also, various psychosomatic disorders, diseases of the digestive system and endocrinopathy were diagnosed most often. The study of stress-regulating systems in children from the anti-terrorist operation zone revealed some differences in the indicators, taking into account the nosology. Thus, patients with cardiovascular patho­logy had an activation of stress-realizing systems, and children with rheumatic diseases — stress of stress-limiting systems. The revealed changes in melatonin level and superoxide dismutase activity in patients with diseases of the circulatory system from the anti-terrorist operation zone indicate an imbalance of enzyme and non-enzyme antioxidants, which can lead to oxidative stress as one of the components of post-traumatic stress disorder. Thus, the obtained data should be taken into account when developing individual programs for medical rehabilitation in children and adolescents with cardiorheumatologic patho­logy from zone of military operations, taking into account the concomitant pathology. Conclusions. Children from the war zone have an imbalance in the components of antioxidant stress responsible for the stress-resistance of the body to damaging factors. The activation of stress-realizing systems in diseases of the circulatory system and the stress of stress-limiting systems in rheumatic diseases have been established.

OBJECTIVES Although several risk factors for outcomes of out-of-hospital cardiac arrest patients have been identified, the cumulative risk of their combinations is not thoroughly clear, especially after targeted temperature management. Therefore, we aimed to develop a risk score to evaluate individual out-of-hospital cardiac arrest patient risk at early admission after targeted temperature management regarding poor neurologic status at discharge. DESIGN Retrospective observational cohort study. SETTING Two large academic medical networks in the United States. PATIENTS Out-of-hospital cardiac arrest survivors treated with targeted temperature management with age of 18 years old or older. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Based on the odds ratios, five identified variables (initial nonShockable rhythm, Leucocyte count 12 K/μL after targeted temperature management, total Adrenalin [epinephrine] ≥ 5 mg, lack of oNlooker cardiopulmonary resuscitation, and Time duration of resuscitation ≥ 20 min) were assigned weighted points. The sum of the points was the total risk score known as the SLANT score (range 0-21 points) for each patient. Based on our risk prediction scores, patients were divided into three risk categories as moderate-risk group (0-7), high-risk group (8-14), and very high-risk group (15-21). Both the ability of our risk score to predict the rates of poor neurologic outcomes at discharge and in-hospital mortality were significant under the Cochran-Armitage trend test (p < 0.001 and p < 0.001, respectively). CONCLUSIONS The risk of poor neurologic outcomes and in-hospital mortality of out-of-hospital cardiac arrest survivors after targeted temperature management is easily assessed using a risk score model derived using the readily available information. Its clinical utility needed further investigation.

Background: Several factors that increase the risk of severe food-induced anaphylaxis have been identified. Objective: We aimed to determine the demographic, etiologic, and clinical features of food-induced anaphylaxis in early childhood and also any other factors associated with severe anaphylaxis. Methods: We carried out a medical chart review of anaphylaxis cases from 16 pediatric allergy and immunology centers in Turkey. Results: The data of 227 patients with 266 food-induced anaphylaxis episodes were included in the study. The median (interquartile range) age of the first anaphylaxis episode was 9 months (6‐18 months); 160 of these patients were boys (70.5%). The anaphylaxis episodes were mild in 75 cases (28.2%), moderate in 154 cases (57.9%), and severe in 37 cases (13.9%). The most frequent food allergens involved were cow's milk (47.4%), nuts (16.7%), and hen's egg (15.8%). Epinephrine was administered in only 98 (36.8%) of these anaphylaxis episodes. A logistic regression analysis revealed two statistically significant factors that were independently associated with severe anaphylaxis: the presence of angioedema and hoarseness during the anaphylactic episode. Urticaria was observed less frequently in patients who developed hypotension. In addition, confusion and syncope were associated with 25.9- and 44.6-fold increases, respectively, in the risk of concomitant hypotension. Conclusion: Cow's milk, nuts, and hen's egg caused the majority of mild and moderate-to-severe anaphylaxis episodes. The presence of angioedema and hoarseness in any patient who presents with a history of food-induced anaphylaxis should alert clinicians that the reaction may be severe. In addition, the presence of confusion, syncope, or stridor probably indicates concomitant hypotension.

Inotropes and inopressors are often first-line treatment in patients with cardiogenic shock. We summarize the pharmacology, indications, and contraindications of dobutamine, milrinone, dopamine, norepinephrine, epinephrine, and levosimendan. We also review the data on the use of these medications for acute decompensated heart failure and cardiogenic shock in this article.

Background/objectives Mastocytosis is a complex disorder presenting with a broad clinical spectrum. In this study, we aimed to evaluate the frequency of systemic symptoms, necessity of the usage of epinephrine autoinjectors (EAI), and factors affecting the use of EAI among pediatric patients with cutaneous mastocytosis (CM). Methods The study population was composed of 53 patients with CM. The clinical data were collected from the medical files. A questionnaire about the patient's anaphylaxis experiences and treatment attitudes toward EAI was performed. Results Thirty-three of 53 patients were male (62.3%), and the median age of the study participants was 80 months. Anaphylaxis was reported in two patients (3.7%). One of the patients had drug-induced anaphylaxis, and the other had venom-induced anaphylaxis. Three patients (5.6%) reported a personal history of EAI use due to systemic symptoms. Patients with higher serum tryptase level and cases of familial mastocytosis had more systemic symptoms (P = .012 and P = .010, respectively). The patient rate of compliance with EAI for prescription filling and carrying the EAI was 88.7% and 79.2% respectively. 41.5% of parents were hesitant to use EAI when necessary, although they were trained for the use of it by medical staff. Conclusions The rate of anaphylaxis in patients with CM in the current study wassignificant and justifies prescribing EAI. Detailed education and counseling on EAI usage are needed to reduce parental hesitancy.

AIM: Adrenaline auto-injector (AAI) dispensing data, a community-based proxy for number of individuals at risk of anaphylaxis, provides complementary information on time trends of anaphylaxis risk in addition to hospital admission data. We examined trends of AAI dispensing over a 10-year period (from January 2005 to December 2014) in Australia. METHODS: Individuals with dispensed AAI were identified from a 10% random sample of Australian Pharmaceutical Benefits Scheme (PBS) data. PBS is the Australian national drug subsidy programme covering all Australians. Cumulative incidence and incidence rates of individuals with AAI were calculated. We assessed difference by age, sex, state and time trends. RESULTS: The cumulative incidence of individuals with AAI in 2005-2014 was 75.43/100 000 (95%CI 75.07-75.80/100 000). Incidence rate of individuals with AAI increased from 2005 to 2014 (from 71.47 to 82.07 per 100 000 person-years) although this varied by state. Over the time assessed, there was a shift to more prescriptions being provided by general practitioners (GP) rather than specialists. Children (0-19 years) were more likely to have been prescribed an AAI from a specialist and adults from a GP. CONCLUSION: Overall, an increase in dispensed AAI mirrored other evidence for a rising prevalence of allergy. This increase could also reflect changes in prescribing practices or increased awareness and education of health-care professionals on anaphylaxis and indications for prescribing AAI. The rising rate of AAI prescribed by GPs compared to decreasing rates by specialists suggests a changing response of the Australian health-care system to the increased burden of anaphylaxis.

Kounis syndrome is an anaphylactic reaction leading to acute coronary syndrome. The acute treatment of anaphylaxis is epinephrine; however, epinephrine may cause coronary vasoconstriction, reduce coronary blood flow, increase myocardial oxygen demand, and worsen myocardial ischemia. On the other hand, coronary vasodilation, a treatment for acute coronary syndrome, can aggravate hypotension in patients with anaphylaxis. Herein, the authors report a case of type II Kounis syndrome, with vasospasm in a patient with coronary disease, requiring the administration of epinephrine and a coronary vasodilator for resuscitation. The authors administered intravenous epinephrine continuously from lower dosages and performed delicate titration. The coronary vasodilator nicorandil, which has little effect on hemodynamics, also was administered. These treatments improved hemodynamics without complications. Circulatory management that considers both anaphylaxis and coronary lesions is crucial to improve prognosis in this syndrome.

ObjectiveIntraosseous access is recommended as a reasonable alternative for vascular access during newborn resuscitation if umbilical access is unavailable, but there are minimal reported data in newborns. We compared intraosseous with intravenous epinephrine administration during resuscitation of severely asphyxiated lambs at birth.MethodsNear-term lambs (139 days’ gestation) were instrumented antenatally for measurement of carotid and pulmonary blood flow and systemic blood pressure. Intrapartum asphyxia was induced by umbilical cord clamping until asystole. Resuscitation commenced with positive pressure ventilation followed by chest compressions and the lambs received either intraosseous or central intravenous epinephrine (10 μg/kg); epinephrine administration was repeated every 3 min until return of spontaneous circulation (ROSC). The lambs were maintained for 30 min after ROSC. Plasma epinephrine levels were measured before cord clamping, at end asphyxia, and at 3 and 15 min post-ROSC.ResultsROSC was successful in 7 of 9 intraosseous epinephrine lambs and in 10 of 12 intravenous epinephrine lambs. The time and number of epinephrine doses required to achieve ROSC were similar between the groups, as were the achieved plasma epinephrine levels. Lambs in both groups displayed a similar marked overshoot in systemic blood pressure and carotid blood flow after ROSC. Blood gas parameters improved more quickly in the intraosseous lambs in the first 3 min, but were otherwise similar over the 30 min after ROSC.ConclusionsIntraosseous epinephrine administration results in similar outcomes to intravenous epinephrine during resuscitation of asphyxiated newborn lambs. These findings support the inclusion of intraosseous access as a route for epinephrine administration in current guidelines.

Introduction. Long-term constant exposure to certain representatives of aliphatic hydrocarbons during the extraction and processing of potash ore can lead to pathological changes on critical organs and systems in production workers. The study aims to evaluate the change in biochemical parameters in workers exposed to chemical production factors (heptane and hexane). Materials and methods. The study of the content of hexane, heptane in the air of the working area and the urine of workers, the establishment of changes in several biochemical (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, glutamyltransferase, epinephrine, and norepinephrine) and general clinical (eosinophils, neutrophils and the eosinophilia index) indicators, modeling of cause-and-effect relationships. Results. Specialists found in the observation group relative to the comparison group: increased levels of heptane and hexane in the urine up to 1.7 times; increased levels of adrenaline and norepinephrine in the blood plasma up to 1.8 times, up to 1.4 times ALAT and γ-GT in the blood serum, up to 1.9 times neutrophils in the nasal secretions associated with increased concentrations of heptane and hexane in the urine; an increase of up to 4.4 times in the frequency of diseases of the nervous system, respiratory organs, and digestion. Conclusions. In the air of the working area of the workers of the flotation shop of the sylvinite processing plant, the concentrations of the studied limit hydrocarbons were below the detection limit; there is an increased concentration of heptane and hexane in the urine. In the workers of the studied production, an increase of 1.4-1.8 times in the level of adrenaline and norepinephrine in blood plasma, 1.2-1.4 times in ALAT and γ-GT in blood serum, 1.9 times in the content of neutrophils in nasal secretions, which characterizes adverse effects from the respiratory, digestive and nervous systems. We proved the dependence of the increased frequency of diseases of the listed organs and systems on the increased concentration of heptane in the urine (R2=0.26-0.43; p=0.0001-0.028).

p53 regulates several signaling pathways to maintain the metabolic homeostasis of cells and modulates the cellular response to stress. Deficiency or excess of nutrients causes cellular metabolic stress, and we hypothesized that p53 could be linked to glucose maintenance. We show here that upon starvation hepatic p53 is stabilized by O-GlcNAcylation and plays an essential role in the physiological regulation of glucose homeostasis. More specifically, p53 binds to PCK1 promoter and regulates its transcriptional activation, thereby controlling hepatic glucose production. Mice lacking p53 in the liver show a reduced gluconeogenic response during calorie restriction. Glucagon, adrenaline and glucocorticoids augment protein levels of p53, and administration of these hormones to p53 deficient human hepatocytes and to liver-specific p53 deficient mice fails to increase glucose levels. Moreover, insulin decreases p53 levels, and over-expression of p53 impairs insulin sensitivity. Finally, protein levels of p53, as well as genes responsible of O-GlcNAcylation are elevated in the liver of type 2 diabetic patients and positively correlate with glucose and HOMA-IR. Overall these results indicate that the O-GlcNAcylation of p53 plays an unsuspected key role regulating in vivo glucose homeostasis., p53 regulates signalling pathways involved in metabolic homeostasis. Here the authors show that O-GlcNAcylation of p53 in the liver plays a key role in the physiological regulation of glucose homeostasis, potentially via controlling the expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase.

To describe the emergency department (ED) triage of anaphylaxis patients based on the Emergency Severity Index (ESI), assess the association between ESI triage level and ED epinephrine administration, and determine characteristics associated with lower acuity triage ESI assignment (levels 3 and 4).We conducted a cohort study of adult and pediatric anaphylaxis patients between September 2010 and September 2018 at an academic ED. Patient characteristics and management were compared between Emergency Severity Index (ESI) triage level 1 or 2 versus levels 3 or 4 using logistic regression analysis. We adhered to STROBE reporting guidelines.A total of 1090 patient visits were included. There were 26 (2%), 515 (47%), 489 (45%), and 60 (6%) visits that were assigned an ESI triage level of 1, 2, 3, and 4, respectively. Epinephrine was administered in the ED to 53% of patients triaged ESI level 1 or 2 and to 40% of patients triaged ESI level 3 or 4. Patients who were assigned a lower acuity ESI level of 3 or 4 had a longer median time from ED arrival to epinephrine administration compared to those with a higher acuity ESI level of 1 or 2 (28 min compared to 13 min, p .001). A lower acuity ESI level was more likely to be assigned to visits with a chief concern of hives, rash, or pruritus (OR 2.33 [95% CI, 1.20-4.53]) and less likely to be assigned to visits among adults (OR, 0.43 [0.31-0.60]), patients who received epinephrine from emergency medical services (OR 0.56 [0.38-0.82]), presented with posterior pharyngeal or uvular angioedema (OR, 0.56 [0.38-0.82]), hypoxemia (OR, 0.34 [0.18-0.64]), or increased heart (OR 0.83 [0.73-0.95]) or respiratory (OR 0.70 [0.60-0.82]) rates.Patients triaged to lower acuity ESI levels experienced delays in ED epinephrine administration. Adult and pediatric patients with skin-related chief concerns were more likely to be to be assigned lower acuity ESI levels. Further studies are needed to identify interventions that will improve ED anaphylaxis triage.

Objectives To examine how postoperative pain control after robotic thoracoscopic surgery varies with liposomal bupivacaine (LipoB) versus 0.5% bupivacaine/1:200,000 epinephrine (Bupi/Epi) intercostal nerve blocks within the context of an enhanced recovery after thoracic surgery (ERATS) protocol. Design A retrospective analysis of a prospectively maintained database of patients undergoing robotic thoracoscopic procedures between September 1, 2018 and October 31, 2019 was conducted. Setting University of Miami, single-institutional. Participants Patients. Interventions Two hundred fifty-two patients had either LipoB intercostal nerve blocks (n = 129) or Bupi/Epi intercostal nerve blocks (n = 123) when undergoing robotic thoracic surgery. Measurements and Main Results Comparative analysis of patient-reported pain levels, in-hospital and post-discharge opioid requirements, 90-day operative complications, length of hospital stay, and hospital costs was performed. Data were stratified to either anatomic lung resection or pulmonary wedge resection/mediastinal-pleural procedures. Bupi/Epi patients reported significantly more acute postoperative pain than LipoB patients, which correlated with higher in-hospital and post-discharge opioid requirements. There were no differences in postoperative complications, length of hospital stay, or hospital costs between the two groups. Conclusions As part of an ERATS protocol, infiltration of intercostal spaces and surgical wounds with LipoB for robotic thoracoscopic procedures afforded better postoperative subjective pain control and decreased opioid requirements without an increase in hospital costs as compared with use of Bupi/Epi.

Background: Patients with platelet dysfunction disorders present with a variety of mucocutaneous bleeding symptoms including easy bruising, frequent epistaxis, bleeding gums upon tooth brushing and for women, heavy menstrual bleeding. Available laboratory assays to evaluate platelet function include the platelet function analyzer (PFA) and in larger centers with coagulation laboratories, light transmission platelet aggregometry (LTA) analyses. Both assays are known to have a number of limitations, especially in the diagnosis of platelet delta granule storage pool deficiency (gamma-SPD).Gamma-SPD is an underdiagnosed condition caused by decreased numbers of platelet dense granules (DGs) and is best diagnosed by electron microscopy (EM). Patients with platelet gamma-SPD have a decreased response to low levels of the agonist adenosine diphosphate (ADP) in the second wave of light transmittance with LTA or decreased ADP secretion by fluorescence lumiaggregometry. There are few reports that have evaluated patients withgamma-SPD and their respective LTA results. One report published in 1987 described normal LTA assays in 23% of patients with gamma-SPD; a more recent report described LTA as having the sensitivity to detect only about 52% of patients with gamma-SPD. The purpose of our study was intended to review the LTA and EM results of patients suspected of having a platelet function disorder at our institution for comparison with previously published studies. Methods: Our study included 344 patients who had been evaluated by both LTA and whole mount EM. Aggregometry utilized five agonists: ADP, epinephrine, collagen, arachidonic acid, and ristocetin. DGs were enumerated in 100 whole-mounted platelets to determine a mean number of dense granules per platelet (DGs/PL). Results: Seventy-seven percent of our patients were found to have gamma-SPD (264/344); 68% (179/264) of these subjects had an abnormal platelet LTA. Thirty-two percent (85/264) of our patients had normal LTA results but were found to have gamma-SPD with a mean of 2.54 ± 0.15 DG/PL (normal = 4 - 6 DG/PL). Conclusion: These data confirm previous reports suggesting the utilization of LTA alone in patients with histories of unexplained bleeding may miss the diagnosis of platelet gamma-SPD. It is, therefore, prudent to assess platelet DG number by EM, especially if platelet LTA assessment is normal. J Hematol. 2021;10(4):196-201 doi: https://doi.org/10.14740/jh832

Background Among patients with a known peanut allergy, previous studies suggest low carrying rates of epinephrine auto-injectors (EAIs) and hesitancy to self-administer epinephrine upon anaphylaxis onset. Given the high prescription rates of epinephrine and prevalence of peanut allergies, it is important to identify rates of on-scene EAI use and affecting factors. Methods The electronic medical records of 217 patients—either with an ED diagnosis of peanut anaphylaxis or diagnosis of anaphylaxis with a known epinephrine prescription from 2010 through May 2020––were reviewed for physician notes and demographic factors. Results Epinephrine was administered on-scene by 25.3% of anaphylaxis patients. Of the 6 health care professionals identified, 100% administered epinephrine on-scene. Females (32.2%) were administered epinephrine on-scene more frequently than males (19.8%; p = 0.04). Rate of epinephrine administration increased from 2010 through 2019 (p = 0.005). Conclusion This study selected for individuals diagnosed with anaphylaxis, meaning EAI use should have been observed nearly 100% of the time. An administration rate of 22.6% observed among individuals not identified as health care professionals suggests that the majority of patients prescribed epinephrine have not used their EAIs, even when presented an opportunity for application. The administration rate of 100% observed among health care professionals indicates that comfort with EAIs facilitates willingness to administer on-scene. EAIs can range up to $900 in expense, thus physicians should employ EAI training devices and other training strategies.