Doses Of Epinephrine Research Articles

Knowledge on anaphylaxis, its associated factors and self-perceived confidence on its management among medical officers attached to the Teaching Hospital Karapitiya

Introduction: Knowledge on anaphylaxis management is paramount in saving lives. The main objective of this study was to assess the knowledge on anaphylaxis, its associated factors and self-perceived confidence on its management among medical officers practising at Teaching Hospital, Karapitiya. Methods: This cross-sectional study included all medical officers (n=531) working in Teaching Hospital Karapitiya. The data were collected within three months via a self-administered questionnaire. The questionnaire consisted of 3 main parts. Part A for demographic data, part B on knowledge on diagnosis and management of anaphylaxis generated from case scenarios and part C on self-perceived confidence on diagnosis and management of anaphylaxis.Results: The response rate was 79% (n=395). Of the respondents, only 9.36% doctors diagnosed all case scenarios correctly. Nearly a quarter (25.8%) identified all anaphylaxis triggers and 25% identified all the amplifying factors. Majority (91.9%) of doctors identified adrenaline as the first line treatment. More than 80% correctly mentioned the second line treatment with more than 90% scored for correct initial management. The score of knowledge on treatment doses of adrenaline in the paediatric age group was poor (60%). Importance of adrenaline auto-injector was identified by 69.1% but knowledge on further follow up of anaphylaxis was sub-optimal. Self-perceived confidence in diagnosis of anaphylaxis 87.6% and the self-perceived confidence in management of anaphylaxis was 83.9%. Conclusions & recommendations: Even though the self-perceived confidence in diagnosis and management of anaphylaxis was satisfactory among the doctors, the knowledge on triggers and amplifying factors were sub-optimal. Novel educational and training strategies must be implemented to overcome the identified deficiencies.

Clinical Features and Outcomes Among Patients With Refractory Out-of-Hospital Cardiac Arrest and an Initial Shockable Rhythm.

Clinical features among patients with refractory out-of-hospital cardiac arrest (OHCA) and initial shockable rhythms of ventricular fibrillation/pulseless ventricular tachycardia are not well-characterized. We compared clinical characteristics and coronary angiographic findings between patients with refractory OHCA (incessant ventricular fibrillation/pulseless ventricular tachycardia after ≥3 direct-current shocks) and those without refractory OHCA. Between 2014 and 2018, a total of 204 patients with ventricular fibrillation/pulseless ventricular tachycardia OHCA (median age 62; males 78%) were divided into groups with (36%, 74/204) and without refractory arrest (64%, 130/204). Refractory OHCA patients had longer cardiopulmonary resuscitation (23 versus 15 minutes), more frequently required ≥450 mg amiodarone (34% versus 3.8%), and had cardiogenic shock (80% versus 55%) necessitating higher adrenaline dose (4.0 versus 1.0 mg) and higher rates of mechanical ventilation (92% versus 74%; all P<0.01). Of 167 patients (82%) selected for coronary angiography, 33% (n=55) had refractory OHCA (P=0.035). Significant coronary artery disease (≥1 major vessel with >70% stenosis) was present in >70% of patients. Refractory OHCA patients frequently had acute coronary occlusion (64% versus 47%), especially left circumflex (20% versus 6.4%) and graft vessel (7.3% versus 0.9%; all P<0.05) compared with those without refractory OHCA. Refractory OHCA group had higher in-hospital mortality (45% versus 30%, P=0.036) and greater new requirement for dialysis (18% versus 6.3%, P=0.011). After adjustment, refractory OHCA was associated with over 2-fold higher odds of in-hospital mortality (odds ratio, 2.28 [95% CI, 1.06-4.89]; P=0.034). Refractory ventricular fibrillation/pulseless ventricular tachycardia OHCA was associated with more intensive resuscitation, higher rates of acute coronary occlusion, and poorer in-hospital outcomes, underscoring the need for future studies in this extreme-risk subgroup.

Impact of the first 24h of continuous kidney replacement therapy on hemodynamics, ventilation, and analgo-sedation in critically ill children.

In a group of children admitted to the paediatric intensive care unit (PICU) receiving continuous kidney replacement therapy (CKRT), we aim to evaluate the data about their hemodynamic, ventilation and analgo-sedation profile in the first 24h of treatment and possible associations with mortality. Retrospective cohort study of children admitted to the PICU of the University Hospital of Padova undergoing CKRT between January 2011 and March 2021. Data was collected at baseline (T0), after 1h (T1) and 24h (T24) of CKRT treatment. The differences in outcome measures were compared between these time points, and between survivors and non-survivors. Sixty-nine patients received CKRT, of whom 38 (55%) died during the PICU stay. Overall, the vasoactive inotropic score and the adrenaline dose increased at T1 compared to T0 (p = 0.012 and p = 0.022, respectively). Compared to T0, at T24 patients showed an improvement in the following ventilatory parameters: Oxygenation Index (p = 0.005), Oxygenation Saturation Index (p = 0.013) PaO2/FiO2 ratio (p = 0.005), SpO2/FiO2 ratio (p = 0.002) and Mean Airway Pressure (p = 0.016). These improvements remained significant in survivors (p = 0.01, p = 0.027, p = 0.01 and p = 0.015, respectively) but not in non-survivors. No changes in analgo-sedative drugs have been described. CKRT showed a significant impact on hemodynamics and ventilation in the first 24h of treatment. We observed a significant rise in the inotropic/vasoactive support required after 1h of treatment in the overall population, and an improvement in the ventilation parameters at 24h only in survivors.

A case of possible anaphylaxis to ASA and structurally unrelated NSAIDs

BackgroundNon-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly used classes of medications, and are among the leading causes of drug hypersensitivity. NSAIDs hypersensitivity reactions are classified by symptom involvement and NSAIDs subclass cross-reactivity. Reactions varying from cutaneous involvement to respiratory symptoms can be triggered by multiple NSAIDs subclasses. Anaphylaxis, while rare, can be induced by a single NSAID, with tolerability of other structurally unrelated subclasses. Reactions that fall outside of these traditional categories are deemed “blended reactions”. We report a unique case of possible anaphylaxis to acetylsalicylic acid (ASA) and ibuprofen, two structurally dissimilar NSAIDs, indicating a severe blended reaction outside of the typical NSAIDs hypersensitivity reaction categories.Case presentationAn otherwise healthy 45 year old woman was referred to the Allergy and Immunology clinic after developing acute onset dyspnea, lip swelling, and generalized urticaria with ibuprofen use requiring treatment with intramuscular epinephrine in the emergency department. She previously tolerated ibuprofen, naproxen, and acetaminophen and had no history of urticaria, angioedema, asthma, or nasal polyps. She underwent an oral challenge to ASA whereby she developed urticaria and throat irritation with rebound symptoms requiring 2 doses of intramuscular epinephrine. On subsequent visits she passed treatment dose acetaminophen and celecoxib challenges. She was counseled to avoid all other NSAIDs and ASA desensitization was offered should this medication be clinically indicated in the future.ConclusionsNSAIDs hypersensitivity reactions can be triggered by individual NSAIDs with tolerance of other subclasses or by multiple structurally unrelated NSAIDs due to COX-1 inhibition. Determining the type of reaction (NERD, NECD, NIUA, SNIUAA, or SNIDHR) allows for appropriate oral challenges and safe alternative therapy recommendations. However, not all clinical reactions fit perfectly into these categories. Patients may also develop blended reactions. Our case highlights a severe blended reaction to multiple unrelated NSAIDs, including likely anaphylaxis to ASA. We note the utility of drug provocation tests (DPTs) to identify safe alternative medication options, as well as the importance of performing DPTs in settings properly equipped to assess and manage severe hypersensitivity reactions including anaphylaxis.

Managing anaphylaxis: Epinephrine, antihistamines, and corticosteroids: More than 10 years of Cross-Canada Anaphylaxis REgistry data

BackgroundEpinephrine is the first-line treatment for anaphylaxis but is often replaced with antihistamines or corticosteroids. Delayed epinephrine administration is a risk factor for fatal anaphylaxis. Convincing data on the role of antihistamines and corticosteroids in anaphylaxis management are sparse. ObjectiveTo establish the impact of prehospital treatment with epinephrine, antihistamines, and/or corticosteroids on anaphylaxis management. MethodsPatients presenting with anaphylaxis were recruited prospectively and retrospectively in 10 Canadian and 1 Israeli emergency departments (EDs) between April 2011 and August 2022, as part of the Cross-Canada Anaphylaxis REgistry. Data on anaphylaxis cases were collected using a standardized form.Primary outcomes were uncontrolled reactions (>2 doses of epinephrine in ED), no prehospital epinephrine use, use of intravenous fluids in ED, and hospital admission. Multivariate regression was used to identify factors associated with primary outcomes. ResultsAmong 5364 reactions recorded, median age was 8.8 years (IQR, 3.78-16.9); 54.9% of the patients were males, and 52.5% had a known food allergy. In the prehospital setting, 37.9% received epinephrine; 44.3% received antihistamines, and 3.15% received corticosteroids. Uncontrolled reactions happened in 250 reactions.Patients treated with prehospital epinephrine were less likely to have uncontrolled reactions (adjusted odds ratio [aOR], 0.955 [95% CI, 0.943-0.967]), receive intravenous fluids in ED (aOR, 0.976 [95% CI, 0.959-0.992]), and to be admitted after the reaction (aOR, 0.964 [95% CI, 0.949-0.980]). Patients treated with prehospital antihistamines were less likely to have uncontrolled reactions (aOR, 0.978 [95% CI, 0.967-0.989]) and to be admitted after the reaction (aOR, 0.963 [95% CI, 0.949-0.977]). Patients who received prehospital corticosteroids were more likely to require intravenous fluids in ED (aOR, 1.059 [95% CI, 1.013-1.107]) and be admitted (aOR, 1.232 [95% CI, 1.181-1.286]). ConclusionOur findings in this predominantly pediatric population support the early use of epinephrine and suggest a beneficial effect of antihistamines. Corticosteroid use in anaphylaxis should be revisited.

Retrieval of Additional Doses of Epinephrine From the New Teva Epinephrine Autoinjector Pen.

Epinephrine autoinjectors are commonly used in urban environments for anaphylaxis. In remote environments, the effects of a single dose of epinephrine may diminish before one can access higher medical care. By retrieving additional epinephrine from common autoinjectors, a medical provider may be able to treat or delay decompensation of anaphylaxis in the field during evacuation. The new Teva epinephrine autoinjectors were obtained. The design of the mechanism was researched by studying patents and disassembling trainers and medication-containing autoinjectors. Multiple methods of access were tried to find the quickest, most reliable method that required minimal tools or equipment. A quick, reliable method of removing the injection syringe from the autoinjector using a knife was determined, as outlined in this article. The syringe plunger had a security design to prevent dispensing further doses from the syringe, so a long narrow object is also required to dispense additional doses. There are 4 additional doses of approximately 0.3-mg epinephrine in these Teva autoinjectors. Prior knowledge of epinephrine equipment and the devices that may be encountered in the field is important for providing life-saving medical care. The ability to retrieve additional doses of epinephrine from a used autoinjector can provide additional life-saving medication while evacuating to a higher level of medical care. This method does carry risks to rescuers and patients; however, it can potentially be life saving.

19: Epinephrine dosing during pediatric extracorporeal cardiopulmonary resuscitation (ECPR): A single center retrospective study assessing adherence to resuscitation guidelines.

19: Epinephrine dosing during pediatric extracorporeal cardiopulmonary resuscitation (ECPR): A single center retrospective study assessing adherence to resuscitation guidelines.

Study on the role of vis (vasoactive - inotropic score) as a predictor of a poor clinical outcome in children after congenital heart surgery with cardiopulmonary bypass

Objectives: Many authors showed that the VIS (vasoactive-inotropic score) has a strong correlation with morbidity and mortality after cardiac surgery in children, but the conclusions are not completely unified. We therefore performed this study to determine the relationship between the VIS score and clinical outcomes in children undergoing cardiac surgery with extracorporeal circulation.&#x0D; Method: Prospective cohort study. A total of 100 pediatric patients from birth to 2 years of age with indications for cardiac surgery with extracorporeal circulation at the Anesthesiology Department of the Heart Institute of Ho Chi Minh City from January 1, 2021, to December 31, 2021, were included in the study. Hourly doses of all vasoactive medications were recorded for the first 48 hours after admission to cardiothoracic intensive care unit and a vaso-active inotropic score was calculated. The VIS scale is calculated by the formula: VIS = dopamine dose (µg/kg/min) + dobutamine dose (µg/kg/min) + 100 × adrenaline dose (µg/kg/min) + 10 × milrinone dose (µg/min) kg/min) + 10000 × vasopressin dose (U/kg/min) + 100 × noradrenaline dose (µg/kg/min). The max and mean values of VIS in the first 24 hours and the max and mean values of VIS in the subsequent 24 hours after admission (from 25th to 48th hour) were calculated.&#x0D; Results: The rate of patients with low cardiac output syndrome was 38.0%. There were 20/100 cases (20.0%) with a poor outcome, of which 19 cases required peritoneal dialysis, 4/100 cases (4.0%) had cardiac arrest, 2/100 cases (2.0%) had seizures, 1/100 (1.0%) had to run ECMO and 4/100 (4.0%) died after surgery. Patients in the high VIS group (mean 48- hour VIS ≥ 11.06) compared with the low VIS group (mean 48- hour VIS &lt; 11.06) were associated with prolonged duration of mechanical ventilation, prolonged CICU length of stay in the ICU, prolonged time to negative fluid balance.&#x0D; Conclusions: The high VIS after surgery was a good predictor of a poor clinical outcome, prolonged duration of mechanical ventilation, prolonged CICU length of stay outcomes in children undergoing cardiac surgery with extracorporeal circulation

The development and validation of a nomogram to determine neurological outcomes in cardiac arrest patients

ObjectivesThis study aimed to investigate the variables that influence neurological functional restoration in cardiac arrest patients and construct a nomogram to predict neurofunctional prognosis.Patients and methodsWe extracted the data from the Dryad database. Associations between patient variables and neurological outcomes were examined by logistic regression models. On the basis of these predictors, a prognostic nomogram was constructed. The identification and calibration of the prognostic nomogram were evaluated through the receiver operating characteristic (ROC) curve, the calibration curve, and the concordance index (C-index).ResultsA total of 374 cardiac arrest individuals were recruited in the research. Sixty percent of the participants had an adverse neurological result. The multivariable logistic regression analysis for poor neurological recovery, which showed patient age ≥ 65 years, previous neurological disease, witnessed arrest, bystander cardio-pulmonary resuscitation(CPR), cardiac arrest presenting with a non-shockable rhythm, total epinephrine dose ≥ 2.5 mg at the time of resuscitation and acute kidney injury(AKI) remained independent predictors for neurological outcomes.ConclusionsThe novel nomogram based on clinical characteristics is an efficient tool to predict neurological outcomes in cardiac arrest patients, which may help clinicians identifying high-risk patients and tailoring personalized treatment regimens.

Pharmacokinetics/pharmacodynamics of epinephrine after single and repeat administration of neffy, EpiPen, and manual intramuscular injection

Epinephrine is the first-line treatment for severe allergic reactions, and rapid treatment is associated with lower rates of hospitalization and death. Current treatment options (epinephrine auto-injectors and manual intramuscular injection) are considered cumbersome, and most patients/caregivers fail to use them, even during severe reactions. An intranasal epinephrine delivery device, neffy, has been designed to provide an additional option for patients/caregivers. We sought to assess the comparative pharmacokinetics and pharmacodynamics of neffy 2.0 mg, EpiPen 0.3 mg, and manual intramuscular injection 0.3 mg. This was a phase 1, randomized, 6-treatment, 6-period, 2-part crossover study in 59 healthy subjects. Pharmacokinetic and pharmacodynamic parameters following single and repeat doses of epinephrine were assessed before dosing and at various postdose intervals. The pharmacokinetic profile of neffy was bracketed by approved injection products, with a mean peak plasma level of 481 pg/mL, which fell between EpiPen (753 pg/mL) and epinephrine manual intramuscular injection (339 pg/mL). When dosed both once and twice, neffy resulted in more pronounced increases in pharmacodynamic parameters relative to EpiPen or manual injection. neffy's pharmacokinetic profile was bracketed by approved injection products, with pharmacodynamic responses that were comparable to or better than approved injection products. neffy is expected to be a safe and effective option, particularly for patients/caregivers who are reluctant to carry and use injection devices.

Early Functional Status Change After Cardiopulmonary Resuscitation in a Pediatric Heart Center: A Single-Center Retrospective Study.

Children with cardiac disease are at significantly higher risk for in-hospital cardiac arrest (CA) compared with those admitted without cardiac disease. CA occurs in 2-6% of patients admitted to a pediatric intensive care unit (ICU) and 4-6% of children admitted to the pediatric cardiac-ICU. Treatment of in-hospital CA with cardiopulmonary resuscitation (CPR) results in return of spontaneous circulation in 43-64% of patients and survival rate that varies from 20 to 51%. We aimed to investigate the change in functional status of survivors who experienced an in-hospital CA using the functional status scale (FSS) in our heart center by conducting a retrospective study of all patients 0-18years who experienced CA between June 2015 and December 2020 in a free-standing university-affiliated quaternary children's hospital. Of the 165 CA patients, 61% (n = 100) survived to hospital discharge. The non-survivors had longer length from admission to CA, higher serum lactate levels peri-CA, and received higher number of epinephrine doses. Using FSS, of the survivors, 26% developed new morbidity, and 9% developed unfavorable outcomes. There was an association of unfavorable outcomes with longer CICU-LOS and number of epinephrine doses given. Sixty-one-percent of CA patients survived to hospital discharge. Of the survivors, 26% developed new morbidity and 91% had favorable outcomes. Future multicenter studies are needed to help better identify modifiable risk factors for development of poor outcomes and help improve outcomes of this fragile patient population.

Severe Anaphylactic Reactions to Home Doses of Oral Immunotherapy for Food Allergy.

Severe anaphylactic reactions to home doses may occur during food allergy oral immunotherapy (OIT). To study the rate and risk factors for such reactions. We studied all patients aged greater than 3.5 years who completed OIT in a single center between April 2010 and January 2020. All home epinephrine-treated reactions (HETRs) were identified. High-grade HETRs (HG-HETRs) were defined as HETRs involving respiratory (SpO2 of 94% or less), cardiovascular (low blood pressure), or central nervous system impairment (loss of consciousness). We investigated the rate and risk factors for HG-HETRs. A total of 1,637 OIT treatments were studied: milk (880), peanut (346), tree nuts (221), sesame (115), and egg (75). Of 390 identified HETRs, 30 HG-HETRs occurred during 27 treatments (1.65% of all treatments). Nearly all (26 of 30) were during milk OIT in patients with house dust mite (HDM) sensitization and asthma (26 of 30 each). Of the 30 patients with HG-HETRs, 21 recovered with one or two epinephrine treatments, but nine (0.55% of all treatments) did not respond to a second dose of epinephrine and were deemed to have refractory anaphylaxis. Three patients required intensive care unit admission and three received epinephrine drip, but none required ventilatory support. Risk factors for HG-HETRs included milk OIT (P= .031), asthma (P= .02) and HDM sensitization (P= .02). No specific triggers for HG-HETR were identified. Of patients with HG-HETRs, 25.9% were fully desensitized, including the four non-milk treated patients; 22.2% were partially desensitized; and 51.9% failed. High-grade HETRs are uncommon, particularly refractory anaphylactic reactions to home OIT doses. Although milk OIT, asthma, and HDM sensitization are the main risk factors for such reactions, identification of patients who are at risk is challenging.

Evaluation of intraoperative bleeding in shoulder arthroscopy with preoperative injection of epinephrine saline: a retrospective comparative study.

Several studies report the positive effects of epinephrine saline irrigation in shoulder arthroscopy3,4,15,18,22,23. Cardiovascular adverse effects have been described1,2,5,6,7,9,19. The Wide Awake Local Anesthesia No Tourniquet (WALANT) limits bleeding13,16,24,25. The aim of this study is to evaluate the effects of epinephrine saline infiltrations of the shoulder on arthroscopic visual comfort. We carried out a retrospective comparative study composed of 2 groups. We included all patients admitted to the department for a rotator cuff surgery. Our exclusion criteria were any other surgical indication and patient refusal. The protocol consisted in making 3 preoperative shoulder infiltrations of 20 ml of epinephrine saline at 0.005 mg/mL. Injections were performed in all patients in group 1 and no specific treatment was performed in group 2 (control group). Data collection was performed the same way in both groups. The main judgment criterion was the evaluation of the surgeon's overall visual comfort using the Visual Analogue Scale (VAS) at the end of the procedure. We also evaluated the intraoperative discomfort related to bleeding every 15 minutes by an objective scale (the Visual Numeric Rating Scale VNRS), as well as the cumulative bleeding time, operating time, the quantity of irrigation fluid used, the blood pressure at the times of the bleeding, the mean blood pressure during the surgery and the presence of thromboembolic and cardiovascular adverse events. We included 30 patients in group 1 and 30 patients in the control group. The mean VAS value at the end of the intervention is significantly higher in group 1 than in the control group: VAS = 10 in group 1 versus VAS = 5 in group 2 (p<0.0001) (higher is better). We also observed a significant decrease in VNRS between the two groups: VNRS = 0.25 in group 1 versus VNRS = 1,00 in group 2 (p<0.0001) (lower is better). Bleeding time was significantly lower in patients in group 1 (1min 39s) compared to patients in group 2 (9min 57s) (p<0.0001). No significant difference was demonstrated concerning the operating times, the quantity of irrigation fluid used and the blood pressure data of the two groups. No adverse effects were observed. The infiltration of low doses of adrenaline as performed in WALANT procedures seems effective in improving visualization in arthroscopy by reducing the bleeding. It can be a simple, efficient, and cost-effective technique with no iatrogenic risk to improve the surgeon's comfort in arthroscopic procedures.

Epinephrine Dosing Use During Extracorporeal Cardiopulmonary Resuscitation: Single-Center Retrospective Cohort.

During pediatric cardiac arrest, contemporary guidelines recommend dosing epinephrine at regular intervals, including in patients requiring extracorporeal membrane oxygenation (ECMO). The impact of epinephrine-induced vasoconstriction on systemic afterload and venoarterial ECMO support is not well-defined. Nested retrospective observational study within a single center. The primary exposure was time from last dose of epinephrine to initiation of ECMO flow; secondary exposures included cumulative epinephrine dose and arrest time. Systemic afterload was assessed by mean arterial pressure and use of systemic vasodilator therapy; ECMO pump flow and Vasoactive-Inotrope Score (VIS) were used as measures of ECMO support. Clearance of lactate was followed post-cannulation as a marker of systemic perfusion. PICU and cardiac ICU in a quaternary-care center. Patients 0-18 years old who required ECMO cannulation during resuscitation over the 6 years, 2014-2020. Patients were excluded if ECMO was initiated before cardiac arrest or if the resuscitation record was incomplete. None. A total of 92 events in 87 patients, with 69 events having complete data for analysis. The median (interquartile range) of total epinephrine dosing was 65 mcg/kg (37-101 mcg/kg), with the last dose given 6 minutes (2-16 min) before the initiation of ECMO flows. Shorter interval between last epinephrine dose and ECMO initiation was associated with increased use of vasodilators within 6 hours of ECMO (p = 0.05), but not with mean arterial pressure after 1 hour of support (estimate, -0.34; p = 0.06). No other associations were identified between epinephrine delivery and mean arterial blood pressure, vasodilator use, pump speed, VIS, or lactate clearance. There is limited evidence to support the idea that regular dosing of epinephrine during cardiac arrest is associated with increased in afterload after ECMO cannulation. Additional studies are needed to validate findings against ECMO flows and clinically relevant outcomes.

Adrenaline-resistant anaphylactic shock caused by contrast medium in a patient after risperidone overdose: a case report

BackgroundIn Japan, the use of risperidone in combination with adrenaline is contraindicated, except in cases of anaphylaxis. Therefore, there is limited clinical evidence regarding the interaction of these two drugs. Here, we report the clinical course of a case of adrenaline-resistant anaphylactic shock induced by a contrast medium injection after a risperidone overdose.Case presentationA man in his 30s was transported to our hospital after attempting suicide by taking 10 mg of risperidone and jumping from a height of 10 m. To determine the location and severity of his injuries, he was injected with an iodinated contrast medium, after which he developed generalized erythema and hypotension and was diagnosed with anaphylactic shock. A 0.5 mg dose of adrenaline was administered with no improvement, followed by another 0.5 mg dose that did not change his blood pressure. After infusion of a sodium bicarbonate solution (8.4%), administration of fresh frozen plasma, and additional administration of adrenaline (0.6–1.2 µg/min), his blood pressure improved, and he recovered from the anaphylactic shock.ConclusionsThis was a rare case of a risperidone overdose followed by adrenaline-resistant anaphylactic shock. The resistance is likely associated with the high blood concentration of risperidone. Our findings indicate that the potential for decreased adrenergic responsiveness should be considered in patients undergoing risperidone treatment in the event of anaphylactic shock.

Active surveillance and clinical analysis of anaphylaxis based on the China Hospital Pharmacovigilance System.

Objective: This study aimed to develop active surveillance programs (ASPs) for anaphylaxis using the China Hospital Pharmacovigilance System (CHPS) and analyze the characteristics, allergens, and management strategies for anaphylaxis within a tertiary hospital setting in China. Methods: We retrospectively analyzed the anaphylaxis cases reported to the National Adverse Drug Reaction Monitoring System in our hospital from 2014 to 2021. Characteristic medical orders, progress notes, and diagnoses in these cases were recorded to identify initial anaphylaxis trigger entries. Based on these initial entries, the questionnaire was developed, and the Delphi method was used to establish consensus entries for anaphylaxis triggers. The CHPS was used to program these trigger entries and construct ASPs, which were then tested on the 238,194 discharged patients to evaluate their performance and analyze the related clinical data. Results: Ten anaphylaxis triggers and three ASPs were ultimately identified. The ASPs captured 309 cases, out of which 94 cases were confirmed as anaphylaxis following manual screening. After removing duplicates, we noted 76 patients who experienced anaphylaxis 79 times. The positive rate of triggers and the positive predictive value of the programs were 0.13% and 30.42%, respectively. The incidence of anaphylaxis in our study was 0.03%, and the number of anaphylaxis cases detected by the ASPs was 5.64 times higher than those detected by the spontaneous reporting system. Anaphylaxis was more common among female patients. Antibacterial drugs, antineoplastic drugs, and contrast media were the most prevalent allergens in clinical practice. Anaphylaxis to antineoplastic drugs had the highest incidence (0.6%) when compared with patients admitted during the same period. Our study revealed a significant underuse of epinephrine and overuse of second-line therapy (glucocorticoids and antihistamines) in the management of anaphylaxis. Furthermore, we found the use and dosage of epinephrine to be inappropriate. Conclusion: The CHPS can effectively utilize both structured and unstructured data to construct anaphylaxis ASPs, and this could counteract the under-reporting by the spontaneous reporting system, the primary adverse reaction monitoring method in China. The treatment and management of anaphylaxis are currently inadequate and require improvement to reduce mortality risk.

Knowledge assessment of radiologists, radiology residents, and radiographers regarding contrast materials and management of adverse drug reactions occurring due to contrast materials: a cross-sectional study.

A questionnaire-based cross-sectional study was conducted from 21 February to 31 March 2019 in five major hospitals of Peshawar, Pakistan. A 30-item questionnaire was adopted from the existing literature containing both open and closed-ended questions and the authors conducted a pilot study among 25 participants to assess the face validity of the tool. A universal sampling technique was adopted. Descriptive statistics were used to summarize the findings of the study. Less than half of the participants could correctly classify iodinated contrast media used in radiology on the basis of ionicity and osmolaity. Sixty-three percent chose severe contrast material-induced allergic reaction as type I hypersensitivity reaction while almost half of them correctly identified the features of iodinated contrast media associated with lesser side effects. Very few of them (6.7%) had read the ACR 2018 manual on contrast media. Regarding the risk factors for acute adverse reactions and signs/symptoms of anaphylaxis few could answer satisfactorily. Twenty-eight percent of participants correctly identified epinephrine as the initial medication in an anaphylactic reaction. Regarding the preferred route of administration, concentration and dose of epinephrine, the participants' correct response was quite poor (43.8%, 6.7%, and 8.6%, respectively). More than 65% of participants could name a single intravenous corticosteroid and antihistamine. Radiology personnel's knowledge regarding contrast material and management of severe contrast material-induced allergic reactions is unsatisfactory.

Poster 163: The Effect of Subacromial Epinephrine Injection on Visualization during Shoulder Arthroscopy

Objectives: Arthroscopic technique is used to treat an increasingly wide variety of pathologic conditions of the shoulder. Adequate visual clarity is imperative for the safety and efficacy of these procedures. Addition of epinephrine to arthroscopic irrigation fluid has been shown to improve surgeon-rated visual clarity, but also increases the cost of the procedure and carries the potential for rare, but serious, cardiovascular adverse events as the total dose increases. We utilize a preoperative subacromial injection containing epinephrine to improve visual clarity during arthroscopic shoulder surgery, thereby limiting the total dose of epinephrine added to the arthroscopic fluid. Methods: We performed a double-blinded, randomized controlled trial (institutional IRB approved and registered with clinicaltrials.gov) to include all adult patients undergoing arthroscopic shoulder surgery requiring visualization of the subacromial space in the seated upright (i.e., beach chair) position. We performed a preoperative injection into the subacromial space with bupivacaine alone for the control group versus a combination of bupivacaine and epinephrine for the study group. Epinephrine was also added to the first fifteen liters of arthroscopic fluid in all patients. Primary outcome was surgeon-rated visual clarity throughout the procedure using the visual analog score (VAS; 1 to 10). A power analysis determined the need for a minimum sample size in each group to ensure adequate power given that the minimal clinically significant difference in visual clarity score has been established in prior studies to be two points. Secondary outcomes included increase in pump pressure during the procedure to improve visualization, total operative time and intraoperative use of blood-pressure modulating medications. We documented any adverse events in the perioperative period in all patients. Results: Sixty patients (n = 60) were enrolled in the study, thirty (n = 30) randomized into each of the study and control groups. Rotator cuff repair was performed in 88% of cases (25 of 30 (83%) study; 28 of 30 (93%) control) with multiple procedures performed in each surgery in 85% of cases (24 of 30 (80%) study; 27 of 30 (90%) control). There was a small improvement in visual clarity that was neither statistically nor clinically significant (8.3 ± 1.4 study versus 7.5 ± 1.9 control, p = 0.09). There was no difference in need for increase in pump pressure to improve visualization (8 of 30 patients (27%) study versus 7 of 30 patients (23%) control, p = 1.0), total operative time (62.1 ± 19.4 min study versus 64.1 ± 31.0 min control, p = 0.86), or intraoperative use of blood-pressure modulating medications (20 of 30 patients (67%) study versus 17 of 30 (57%) control, p = 0.6). There were no perioperative adverse events in either the study or control group. Conclusions: Performing a preoperative injection of epinephrine into the subacromial space results in a small improvement in visual clarity that is neither statistically nor clinically significant during arthroscopic shoulder surgery. There was no difference in any of the secondary outcomes, including change in pump pressure to improve visualization, total operative time, or intraoperative use of blood- pressure modulating medications. However, there were no adverse events in either group, suggesting that the addition of a preoperative epinephrine injection is safe to perform.

Cyclic-AMP response element binding protein (CREB) and microRNA miR-29b regulate renalase gene expression under catecholamine excess conditions

AimsRenalase, a key mediator of cross-talk between kidneys and sympathetic nervous system, exerts protective roles in various cardiovascular/renal disease states. However, molecular mechanisms underpinning renalase gene expression remain incompletely understood. Here, we sought to identify the key molecular regulators of renalase under basal/catecholamine-excess conditions. Materials and methodsIdentification of the core promoter domain of renalase was carried out by promoter-reporter assays in N2a/HEK-293/H9c2 cells. Computational analysis of the renalase core promoter domain, over-expression of cyclic-AMP-response-element-binding-protein (CREB)/dominant negative mutant of CREB, ChIP assays were performed to determine the role of CREB in transcription regulation. Role of the miR-29b-mediated-suppression of renalase was validated in-vivo by using locked-nucleic-acid-inhibitors of miR-29. qRT-PCR and Western-blot analyses measured the expression of renalase, CREB, miR-29b and normalization controls in cell lysates/ tissue samples under basal/epinephrine-treated conditions. Key findingsCREB, a downstream effector in epinephrine signaling, activated renalase expression via its binding to the renalase-promoter. Physiological doses of epinephrine and isoproterenol enhanced renalase-promoter activity and endogenous renalase protein level while propranolol diminished the promoter activity and endogenous renalase protein level indicating a potential role of beta-adrenergic receptor in renalase gene regulation. Multiple animal models (acute exercise, genetically hypertensive/stroke-prone mice/rat) displayed directionally-concordant expression of CREB and renalase. Administration of miR-29b inhibitor in mice upregulated endogenous renalase expression. Moreover, epinephrine treatment down-regulated miR-29b promoter-activity/transcript levels. SignificanceThis study provides evidence for renalase gene regulation by concomitant transcriptional activation via CREB and post-transcriptional attenuation via miR-29b under excess epinephrine conditions. These findings have implications for disease states with dysregulated catecholamines.

Factors associated with circulatory death after out-of-hospital cardiac arrest: a population-based cluster analysis

BackgroundOut-of-hospital cardiac arrest (OHCA) is a common cause of death. Early circulatory failure is the most common reason for death within the first 48 h. This study in intensive care unit (ICU) patients with OHCA was designed to identify and characterize clusters based on clinical features and to determine the frequency of death from refractory postresuscitation shock (RPRS) in each cluster.MethodsWe retrospectively identified adults admitted alive to ICUs after OHCA in 2011–2018 and recorded in a prospective registry for the Paris region (France). We identified patient clusters by performing an unsupervised hierarchical cluster analysis (without mode of death among the variables) based on Utstein clinical and laboratory variables. For each cluster, we estimated the hazard ratio (HRs) for RPRS.ResultsOf the 4445 included patients, 1468 (33%) were discharged alive from the ICU and 2977 (67%) died in the ICU. We identified four clusters: initial shockable rhythm with short low-flow time (cluster 1), initial non-shockable rhythm with usual absence of ST-segment elevation (cluster 2), initial non-shockable rhythm with long no-flow time (cluster 3), and long low-flow time with high epinephrine dose (cluster 4). RPRS was significantly associated with this last cluster (HR, 5.51; 95% confidence interval 4.51–6.74).ConclusionsWe identified patient clusters based on Utstein criteria, and one cluster was strongly associated with RPRS. This result may help to make decisions about using specific treatments after OHCA.