[Prehospital care of anaphylactic reactions by the air rescue and ground-based emergency services Dresden : An analysis of treatment and outcome]. / Präklinische Versorgung von anaphylaktischen Reaktionen durch die Dresdner Luft- und Bodenrettung : Analyse von Therapie und Outcome.

BACKGROUND: Anaphylaxis can lead to a life-threatening situation. Therefore, rapid diagnosis and emergency treatment is indicated. Immediate treatment with intramuscular adrenaline (or intravascularly with sufficient medical expertise) in anaphylaxis with cardiovascular and/or respiratory symptoms is recommended by various guidelines. Previous studies have shown that anaphylaxis is often not treated according to guidelines and that adrenaline in particular is rarely administered. OBJECTIVE: The aim of the study was to investigate the data on emergency treatment and outcomes of patients with anaphylaxis by the air rescue and ground-based emergency services Dresden. Moreover, the results of the air- and ground-based services were compared. The focus was on administration of adrenaline and outcomes. MATERIALS AND METHODS: Data from the ground-based emergency service Dresden (from 2012 to 2016) and the air rescue service Dresden (from 2008 to 2015) related to anaphylactic reactions were analyzed retrospectively. The severity of the anaphylaxis, the emergency medication administered, further monitoring, and outcomes were analyzed. RESULTS: Data from 152 adults/29 children were analyzed for air rescue and 1131 adults/223 children for the ground-based emergency service. Adults with grade II-IV anaphylaxis received adrenaline in 19% (air rescue) and 7% (ground rescue) of cases. Children with grade II-IV anaphylaxis received adrenaline in 7% (air rescue) and 8% (ground rescue) of cases. Immediate drug therapy led to an improvement in general condition in 96-98% (air rescue) and 72-77% (ground-based emergency service) of cases. A significant correlation was found between the administration of adrenaline and the improvement in outcome in the ground-based emergency cohort. CONCLUSION: Guideline-compliant first-line therapy with adrenaline was not performed in the majority of the cases analyzed in this study. The significant effect of adrenaline on outcome demonstrated in this study emphases the need to improve the emergency treatment of anaphylactic reactions.

A retrospective, multi-agency 'target trial emulation' for the comparison of post-resuscitation epinephrine to norepinephrine.

INTRODUCTION: Epinephrine and norepinephrine are the two most commonly used prehospital vasopressors in the United States. Prior studies have suggested that use of a post-ROSC epinephrine infusion may be associated with increased rearrest and mortality in comparison to use of norepinephrine. We used target trial emulation methodology to compare the rates of rearrest and mortality between the groups of OHCA patients receiving these vasopressors in the prehospital setting. METHODS: Adult (18-80 years of age) non-traumatic OHCA patients in the 2018-2022 ESO Data Collaborative datasets with a documented post-ROSC norepinephrine or epinephrine infusion were included in this study. Logistic regression modeling was used to evaluate the association between vasopressor agent and outcome using two sets of covariables. The first set of covariables included standard Utstein factors, the dispatch to ROSC interval, the ROSC to vasopressor interval, and the follow-up interval. The second set added prehospital systolic blood pressure and SpO2 values. Kaplan-Meier time-to-event analysis was also conducted and the vasopressor groups were compared using a multivariable Cox regression model. RESULTS: Overall, 1,893 patients treated by 309 EMS agencies were eligible for analysis. 1,010 (53.4%) received an epinephrine infusion and 883 (46.7%) received a norepinephrine infusion as their initial vasopressor. Adjusted analyses did not discover an association between vasopressor agent and rearrest (aOR: 0.93 [0.72, 1.21]) or mortality (aOR: 1.00 [0.59, 1.69]). CONCLUSIONS: In this multi-agency target trial emulation, the use of a post-resuscitation epinephrine infusion was not associated with increased odds of rearrest in comparison to the use of a norepinephrine infusion.

Australian and New Zealand Anaesthetic Allergy Group/Australian and New Zealand College of Anaesthetists perioperative anaphylaxis management guideline 2022.

Perioperative anaphylaxis is a potentially life-threatening emergency that requires prompt recognition and institution of life-saving therapy. The Australian and New Zealand College of Anaesthetists and Australian and New Zealand Anaesthetic Allergy Group have partnered to develop the anaphylaxis management guideline along with crisis management cards that are recommended for use in suspected anaphylaxis in the perioperative setting. This is the third version of these guidelines with the second version having been published in 2016. This article contains the revised Australian and New Zealand Anaesthetic Allergy Group/Australian and New Zealand College of Anaesthetists perioperative anaphylaxis management guideline, with a brief review of the current evidence for the management of anaphylaxis in the perioperative environment.

The confidence and competence of primary school staff to administer an adrenaline auto-injector.

School teachers are often inadequately prepared to use an adrenaline auto-injector (AAI), resulting in potentially dangerous treatment delays. The purpose of this study was to assess the observed competence, and self-reported confidence, of primary school teachers in the Republic of Ireland (RoI) to use an AAI. An evaluation of whether there was a link between confidence and competence was also assessed. Teachers from four primary schools in the RoI completed a questionnaire to assess their prior level of experience, training, and confidence levels with AAI administration. The four steps in administrating trainer AAI to a mannequin simulator were then assessed. A total of 61 teachers participated (out of a population of 80). The mean self-reported confidence was 1.82 out of 5 (SD = 0.96). There was no significant difference in confidence between trained and untrained participants (U = 240.5, NS). Participants who had received AAI administration training performed significantly more of the steps correctly (mean = 3.85, SD = 0.95) as compared to those who had received no training (mean = 2.97, SD = 1.10; U = 180.5, p = 0.008). There was no correlation between confidence in administrating AAI and the percentage of steps in the procedure performed correctly (rho = -0.17, NS).  Conclusion: Improvements in readiness to administer AAIs can be achieved through the application of more effective approaches to teaching clinical skills, changes to school policies and practices, and consideration of the design of AAIs in order to make their operation safer and simpler. It is important that teachers have the confidence and competence to safely administer an AAI. What is Known: • Poor ability in adrenaline auto-injector use seen across population groups-healthcare professionals, patients, carers, and school staff • Training in the use of adrenaline auto-injectors has positive impact on competency What is New: • Irish school teachers show poor levels of competency in adrenaline auto-injector use • No observed correlation between reported confidence and competency.

Anatomical and functional changes of the fetal adrenal gland in intrauterine growth restriction.

OBJECTIVE: The aim of this study was to demonstrate the establishment of adrenal sparing in intrauterine growth restricted (IUGR) human fetuses. IUGR fetuses are a subgroup of small for gestational age (SGA) fetuses that are unable to reach their own growth potential because of chronic hypoxia and undernutrition. We hypothesized that in IUGR fetuses the adrenal gland is relatively larger and secretion of noradrenaline (NA), adrenaline (A), and cortisol is increased. STUDY DESIGN: This is a prospective observational study including 65 singleton pregnancies (42 IUGR and 23 controls). Using two-dimensional ultrasound, we measured fetal adrenal diameters and adrenal/abdominal circumference (AD/AC) ratio between 25 and 37 weeks. We considered only one measurement per fetus. In 21 pregnancies we also measured NA, A, and cortisol levels in arterial and venous fetal cord blood collected at the time of delivery. RESULTS: The AD/AC ratio was significantly higher in IUGR fetuses than in controls. Cord NA and A levels were significantly higher in IUGR fetuses than in controls. An increase in cortisol secretion in IUGR fetuses was observed but the difference was not statistically significant. CONCLUSIONS: Adrenal sparing correlates with a relative increase in adrenal measurements and function.

Tranexamic acid versus adrenaline-soaked pledgets for the reduction of intraoperative bleeding in functional endoscopic sinus surgery.

OBJECTIVE: Aim: To examine the impact of locally applied tranexamic acid and adrenaline, separately and in combination, on intraoperative blood loss and surgical field quality during functional endoscopic sinus surgery. PATIENTS AND METHODS: Materials and Methods: The study involved 40 patients with chronic rhinosinusitis. They were divided into two groups. Group I received adrenaline alone in one side and a mixture of adrenaline and tranexamic acid in the other side. Group II received adrenaline alone in one side and tranexamic acid in the otherside. Parameters like surgery time, blood loss, and surgical field quality were studied. RESULTS: Results: In Group I, the combination of adrenaline and tranexamic acid significantly reduced blood loss and enhanced surgical field quality compared to adrenaline alone. In Group II, adrenaline outperformed tranexamic acid in shortening surgery duration and improving surgical field quality. However, there was no significant difference in blood loss reduction between adrenaline and tranexamic acid. CONCLUSION: Conclusions: The study concluded that tranexamic acid is less effective than adrenaline when introduced as topical intranasal pledgets in both decreasing the time needed for the surgery and improving the subjective satisfaction of the surgeon while there is no significant difference regarding decreasing intraoperative blood loss. The mixture of adrenaline and tranexamic acid pledgets are more effective than adrenaline-only pledgets in terms of decreasing the intraoperative blood loss and improving the surgeon's satisfaction with no significant difference regarding the time needed for the surgery.

Blockage of metallothionein synthesis via adrenaline ß receptor activation invalidates dehydroeffusol-mediated prevention of amyloid ß1-42 toxicity.

Dehydroeffusol, a major phenanthrene in Juncus effusus, protects neurodegeneration induced by intracellular Zn2+ ferried by extracellular amyloid ß1-42 (Aß1-42). Here we focused on adrenaline ß receptor activation and the induction of metallothioneins (MTs), intracellular Zn2+-binding proteins to test the protective mechanism of dehydroeffusol. Isoproterenol, an agonist of adrenergic ß receptors elevated the level of MTs in the dentate granule cell layer 1 day after intracerebroventricular (ICV) injection. When Aß1-42 was injected 1 day after isoproterenol injection, pre-injection of isoproterenol protected Aß1-42 toxicity via reducing the increase in intracellular Zn2+ after ICV injection of Aß1-42. On the basis of the effect of increased MTs by isoproterenol, dehydroeffusol (15 mg/kg body weight) was orally administered to mice once a day for 2 days. On day later, dehydroeffusol elevated the level of MTs and prevented Aß1-42 toxicity via reducing Aß1-42-mediated increase in intracellular Zn2+. In contrast, propranolol, an antagonist of adrenergic ß receptors reduced the level of MTs increased by dehydroeffusol, resulting in invalidating the preventive effect of dehydroeffusol on Aß1-42 toxicity. The present study indicates that blockage of MT synthesis via adrenaline ß receptor activation invalidates dehydroeffusol-mediated prevention of Aß1-42 toxicity. It is likely that MT synthesis via adrenaline ß receptor activation is beneficial to neuroprotection and that oral intake of dehydroeffusol preventively serves against the Aß1-42 toxicity.

Study on the Mechanism of the Adrenaline-Evoked Procoagulant Response in Human Platelets.

Adrenaline has recently been found to trigger phosphatidylserine (PS) exposure on blood platelets, resulting in amplification of the coagulation process, but the mechanism is only fragmentarily established. Using a panel of platelet receptors' antagonists and modulators of signaling pathways, we evaluated the importance of these in adrenaline-evoked PS exposure by flow cytometry. Calcium and sodium ion influx into platelet cytosol, after adrenaline treatment, was examined by fluorimetric measurements. We found a strong reduction in PS exposure after blocking of sodium and calcium ion influx via Na+/H+ exchanger (NHE) and Na+/Ca2+ exchanger (NCX), respectively. ADP receptor antagonists produced a moderate inhibitory effect. Substantial limitation of PS exposure was observed in the presence of GPIIb/IIIa antagonist, phosphoinositide-3 kinase (PI3-K) inhibitors, or prostaglandin E1, a cyclic adenosine monophosphate (cAMP)-elevating agent. We demonstrated that adrenaline may develop a procoagulant response in human platelets with the substantial role of ion exchangers (NHE and NCX), secreted ADP, GPIIb/IIIa-dependent outside-in signaling, and PI3-K. Inhibition of the above mechanisms and increasing cytosolic cAMP seem to be the most efficient procedures to control adrenaline-evoked PS exposure in human platelets.

Prehospital and In-Hospital Treatment with Adrenaline and Related Prognosis in Anaphylaxis Patients.

INTRODUCTION: Although intramuscular adrenaline is the recommended first-line treatment for anaphylaxis, not all patients receive this treatment. The consequences in daily clinical practice are sparsely described. This study aimed to investigate the treatment administered to anaphylactic patients and the related prognosis. METHODS: A retrospective register-based study of patients with anaphylaxis referred to the allergy centre, Odense University Hospital (2019-2021). Each patient's medical records were reviewed for contacts with the emergency departments and the prehospital emergency medical service in the Region of Southern Denmark. The World Allergy Organization (WAO) grading system was used to assess the severity of prehospital and in-hospital anaphylaxis. Furthermore, the treatment administered to the patients was registered. RESULTS: In total, 315 patients were included. The prehospital system had contact with 256 of these patients (two were released prehospitally following treatment and 12 patients had insufficient data to assess anaphylaxis). Of the remaining 242 patients, 115 had anaphylaxis prehospitally (WAO grades 3-5); 59% (67/115) received adrenaline. Among the 67 patients who received prehospital adrenaline, 9 patients (13.4%; 95% CI: 6.3-24.0%) still had anaphylaxis at arrival at the emergency department. Of the 48 patients that were not treated with prehospital adrenaline, 17 patients (35.5%; 95% CI: 22.1-50.5) had anaphylaxis at the arrival to the emergency department. Among the 127 patients without prehospital anaphylaxis (WAO grades 0-2), 22 patients (18.2%; 95% CI: 11.8-26.2%) who did not receive prehospital adrenaline had anaphylaxis at arrival to the emergency department, while none of the 6 patients treated prehospitally with adrenaline had anaphylaxis. CONCLUSION: Omission of prehospital adrenaline in anaphylactic patients is associated with more severe anaphylactic symptoms at arrival to the hospital. Adrenaline treatment remains suboptimal since only half of the patients received prehospital adrenaline and only 1 out of 4 patients, with clinical signs of anaphylaxis, received adrenaline inside the hospital.

Disparities in pediatric anaphylaxis triggers and management across Asia.

BACKGROUND: The epidemiology and management of anaphylaxis are not well-reported in Asia. METHODS: A regional pediatric anaphylaxis registry was established by the Asia-Pacific Research Network for Anaphylaxis (APRA), using standardized protocols for prospective data collection, to evaluate the triggers and management of anaphylaxis in the Asia-Pacific region. Pediatric patients below 18 years presenting with anaphylaxis across four Asian countries/cities (Thailand, Singapore, Hong Kong (HK), and Qingdao) were included. Allergen triggers, symptoms, anaphylaxis severity, and management were compared. RESULTS: Between 2019 and 2022, 721 anaphylaxis episodes in 689 patients from 16 centers were identified. The mean age at anaphylaxis presentation was 7.0 years (SD = 5.2) and 60% were male. Food was the most common trigger (62%), particularly eggs and cow's milk in children aged 3 years and below. In school-age children, nut anaphylaxis was most common in HK and Singapore, but was rare in the other countries, and wheat was the top allergen in Bangkok. Shellfish anaphylaxis was most common in children aged 7-17. Adrenaline was administered in 60% of cases, with 9% given adrenaline before hospital arrival. Adrenaline devices were prescribed in up to 82% of cases in Thailand but none in Qingdao. CONCLUSIONS: The APRA identified food as the main trigger of anaphylaxis in children, but causative allergens differed even across Asian countries. Fewer than two-thirds of cases received adrenaline treatment, pre-hospital adrenaline usage was low, and adrenaline device prescription remained suboptimal. The registry recognizes an unmet need to strengthen anaphylaxis care and research in Asia-Pacific.

Effectiveness of perineural administration of dexamethasone with lidocaine on onset time of sensory block and early postoperative analgesia in axillary brachial plexus block: a prospective cohort study, Ethiopia.

Introduction: The axillary brachial plexus block is a popular nerve block for forearm, wrist, and hand surgery. The aim of this study was to assess the effectiveness of perineural administration of dexamethasone as an adjunct to lidocaine with adrenaline on the onset of sensory block and early postoperative analgesia in trans-arterial axillary brachial plexus block. Methodology: This single-centered prospective cohort study recruited 68 adult patients, 34 in each groups. The frequently used 8 mg dexamethasone combined with 1% lidocaine and adrenaline was investigated. The normality of the data was checked using the Shapiro-Wilk test. An independent t-test was used to compare the mean values of symmetric numeric data. Categorical variables between the two groups were analyzed using χ2. The Mann-Whitney U test and Kaplan-Meier method using the log-rank test were used to compare asymmetric numeric data, and a P-value of <0.05 was considered as significant. Results: The median onset time of sensory block was comparable between the nonexposed (24(6) min) and exposed group (24(6) min) (P=0.068). However, the duration of sensory block was significantly longer in the exposed group (235.5±37.51 min) than the nonexposed group (172.76±28.19 min) (P<0.001). The time to the first analgesic request was significantly longer in the exposed than the nonexposed group (P<0.01). Postoperative pain scores were significantly lower at 4 and 8 h in the exposed group (P<0.05). Conclusion and recommendations: The addition of 8 mg dexamethasone to 1% lidocaine with adrenaline solution in trans-arterial axillary brachial plexus block for ambulatory elective hand, wrist, and forearm surgeries prolonged the duration of sensory blockade and the first analgesic request time but did not reduce the onset time of sensory block. The authors recommend the addition of 8 mg dexamethasone to 1% lidocaine with adrenaline solution to prolong the duration of sensory block and the first analgesic request time.

El pediatra de Atención Primaria y la anafilaxia / The primary care pediatrician and anaphylaxis

La anafilaxia es una reacción alérgica grave de instauración rápida y potencialmente mortal. El diagnóstico de anafilaxia es clínico y debe realizarse de manera precoz. Aparece en las 2 primeras horas tras exposición al alérgeno, en los primeros 30 minutos en alergia alimentaria y más precozmente con medicamentos intravenosos o picaduras de himenópteros. Los síntomas cutáneos suelen ser los primeros en manifestarse y están presentes en la mayoría de los casos, más de un 80%. Pueden ser leves o transitorios e incluso no estar presentes en un 18% de los casos. Si se afecta el sistema cardiocirculatorio estaríamos ante un shock anafiláctico. La causa más frecuente en Pediatría son los alimentos. Existen cofactores cuya presencia aumenta la probabilidad de anafilaxia; los más importantes son: el ejercicio, los fármacos, la fiebre y el estrés. El tratamiento de elección es la adrenalina intramuscular. Tanto los padres como los niños deben saber identificar los signos y/o síntomas del inicio de la anafilaxia para instaurar el tratamiento pautado en el plan de acción escrito.

Anaphylaxis is a severe, rapid and potentially fatal allergic reaction. The diagnosis of anaphylaxis is clinical and must be early. It appears in the first 2 hours after exposure to the allergen, in the first 30 minutes in food allergy and earlier with intravenous drugs or hymenoptera stings. Cutaneous symptoms are generally the first to appear and are present in most cases, more than 80%. They may be mild or transitory, or absent in 18% of cases. If the cardio-circulatory system is affected, an anaphylactic shock occurs. The most frequent cause in pediatrics is nutrition. There are several cofactors whose presence increases the likelihood of anaphylaxis; the most important are: exercise, medication, fever and stress. The treatment of choice is intramuscular adrenaline. Parents and children should be able to identify the signs and/or symptoms of anaphylaxis in order to implement the treatment prescribed in the written action plan. (AU)

α1 and ß3 adrenergic receptor-mediated excitatory effects of adrenaline on the caudal neurosecretory system (CNSS) in olive flounder, Paralichthys olivaceus.

Adrenaline is one of the most important neurotransmitters in the central nervous system and is produced during stress. In this study, we investigated the modulatory role of adrenaline and adrenergic receptors on the neuroendocrine Dahlgren cells in the caudal neurosecretory system (CNSS) of olive flounder. Ex vivo electrophysiological recordings revealed that adrenaline significantly increased the firing frequency and altered the firing pattern of Dahlgren cells. Moreover, treatment with adrenaline led to a significant upregulation of ion channels and major hormone secretion genes in CNSS at the mRNA levels. Additionally, treatment with adrenaline resulted in a significantly elevation in the expression levels of α1- and ß3-adrenergic receptors. Furthermore, the ß3-adrenergic receptor antagonist exerts a significant inhibitory effect on adrenaline-induced enhancement firing activities of Dahlgren cells, whereas the α1-adrenergic receptor antagonist displays a comparatively weaker inhibitory effect. Additionally, the enhanced firing activity induced by adrenaline could be effectively suppressed by both α1- and ß3-adrenergic receptor antagonists. Taken together, these findings provide strong evidence in favor of the excitatory effects of adrenaline through α1 and ß3 adrenergic receptors in CNSS to stimulate the secretion of stress-related hormones, ß3-adrenergic receptor plays a more dominant role in the modulation of firing activities of Dahlgren cells by adrenaline and thereby regulates the stress response in olive flounder.

Evaluation of the origin and educational quality of youtube videos on adrenaline auto-injectors.

Summary: Background. Guidelines highlight the pivotal role of adrenaline auto-injector (AAI) training. However, the standards of visual training platforms has not been determined. Our aim was to evaluate the reliability and quality of the AAI related videos on YouTube. Methods. After a search on YouTube about AAI, all videos were categorized into groups based on their origin and the aim of the content. The quality, reliability, understandibility, and actionability of the videos were evaluated using the Global Quality Scale (GQS), Patient Education Materials Assessment Tool Audovisiual (PEMAT-A/V), Quality Criteria for Consumer Health Information (DISCERN), and a modified DISCERN. In each video, the application steps of AAI were evaluated according to a scale of correct usage. Results. 107 YouTube videos in English were included. No significant difference in terms of views, likes, duration and uploading time was observed between the health and non-health groups whereas the GQS (p=0.001), DISCERN (total: p=0.02, and overall: p=0.094), modified DISCERN (p=0.001) scores were higher in the health group. It was found that scores tended to be higher in educational videos. AAI use was mentioned in 85% videos. The median number of mentioned steps was 6. Conclusions. YouTube is an effective platform for visual learning for the use of AAIs. Although the visibility of the videos is equal independent of the origin, the ones recorded by medical professionals seem to provide the most qualified and reliable information.

Maternal and neonatal cortisol and catecholamines throughout vaginal eutocia and C-section in dogs.

Increased fetal cortisol is associated with catecholamine release, a primary factor for neonatal adaptive responses. However, relationship between canine peripartum cortisol and catecholamine is unknown. We aimed to compare serum adrenaline, noradrenaline and cortisol during peripartum in bitches and neonates of distinct obstetric conditions and to assess amniotic fluid cortisol concentration. Twenty females and maximum of three puppies per litter were allocated into Vaginal Eutocia (10 females; 17 neonates) and Elective C-section (10 females; 20 neonates) groups. Amniotic fluid was collected at delivery for cortisol concentration. Maternal and neonatal blood were collected prepartum, intrapartum, postpartum and 1h postpartum, and at birth, 30 and 60min, 12hs and 24hs, respectively, for cortisol, adrenaline and noradrenaline assessment. C-section determined higher noradrenaline throughout delivery and cortisol concentration from intrapartum through 1h postpartum, compared to vaginal birth. C-section maternal cortisol showed progressive increase from intrapartum onwards, while neonatal cortisol remained unchanged. No difference of maternal cortisol concentration occurred along whelping, whereas a significant decrease was verified for vaginal delivery puppies from birth until the 12hs. Puppies delivered vaginally had higher cortisol concentration at birth and 30min, compared to c-section puppies. There was a higher concentration of amniotic fluid cortisol in vaginal eutocia. In conclusion, c-section induces higher maternal stress during and after surgery, whilst vaginal delivery is a more neonatal physiologically stressful condition, contributing to better adaptation during transition.

Emergency treatment of peri-operative anaphylaxis: Resuscitation Council UK algorithm for anaesthetists.

Peri-operative anaphylaxis is a rare but potentially catastrophic event which must be considered whenever unexpected and significant cardiovascular or respiratory compromise occurs during anaesthesia. The Resuscitation Council UK algorithm for peri-operative anaphylaxis highlights the importance of early intravenous adrenaline and fluid resuscitation and provides guidance on the treatment of refractory anaphylaxis and immediate follow-up. This algorithm is endorsed by the Royal College of Anaesthetists, Association of Anaesthetists, British Society of Allergy and Clinical Immunology and Clinical Immunology Professional Network of the British Society for Immunology. This document was produced by the Perioperative Allergy Network steering committee in collaboration with the Resuscitation Council UK.

Anaphylaxis mortality in the perioperative setting: Epidemiology, elicitors, risk factors and knowledge gaps.

Perioperative anaphylaxis (PA) is a severe condition that can be fatal, but data on PA mortality are scarce. The aim of this article is to review the epidemiology, elicitors and risk factors for PA mortality and identify knowledge gaps and areas for improvement regarding the management of severe PA. PA affects about 100 cases per million procedures. Mortality is rare, estimated at 3 to 5 cases per million procedures, but the PA mortality rate is higher than for other anaphylaxis aetiologies, at 1.4% to 4.8%. However, the data are incomplete. Published data mention neuromuscular blocking agents and antibiotics, mainly penicillin and cefazolin, as the main causes of fatal PA. Reported risk factors for fatal PA vary in different countries. Most frequently occurring comorbidities are obesity, male gender, cardiovascular diseases and ongoing treatment with beta-blockers. However, there are no clues about how these factors interact and the impact of individual risk factors. The pathophysiology of fatal PA is still not completely known. Genetic factors such as deficiency in PAF-acetyl hydrolase and hereditary alpha-tryptasemia, have been reported as modulators of severe anaphylaxis and possible targets for specific treatments. Our review underlines unmet needs in the field of fatal PA. Although we confirmed the need for timely administration of an adequate dose of adrenaline and the proper infusion of fluids, there is no evidence-based data on the proper dose of intravenous titrated adrenaline and which clinical manifestations would flag the need for fluid therapy. There are no large clinical studies supporting the administration of alternative vasopressors, such as glucagon and methylene blue. Further research on pathophysiological mechanisms of PA and its severity may address these issues and help clinicians to define new therapeutic approaches.