Showing papers on "Epinephrine published in 2019"

A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest

Abstract: METHODS In a randomized, double-blind trial involving 8014 patients with out-of-hospital cardiac arrest in the United Kingdom, paramedics at five National Health Service ambulance services administered either parenteral epinephrine (4015 patients) or saline placebo (3999 patients), along with standard care. The primary outcome was the rate of survival at 30 days. Secondary outcomes included the rate of survival until hospital discharge with a favorable neurologic outcome, as indicated by a score of 3 or less on the modified Rankin scale (which ranges from 0 [no symptoms] to 6 [death]).

Acne and Stress: Impact of Catecholamines on Cutibacterium acnes.

Abstract: Cutibacterium acnes (former Propionibacterium acnes), is a bacterium characterized by high genomic variability, consisting of four subtypes and six major ribotypes. Skin is the largest neuroendocrine organ of the human body and many cutaneous hormones and neurohormones can modulate bacterial physiology. Here, we investigated the effect of catecholamines, i.e., epinephrine and norepinephrine, on two representative strains of C. acnes, of which the genome has been fully sequenced, identified as RT4 acneic and RT6 non-acneic strains. Epinephrine and norepinephrine (10-6 M) had no impact on the growth of C. acnes but epinephrine increased RT4 and RT6 biofilm formation, as measured by crystal violet staining, whereas norepinephrine was only active on the RT4 strain. We obtained the same results by confocal microscopy with the RT4 strain, whereas there was no effect of either catecholamine on the RT6 strain. However, this strain was also sensitive to catecholamines, as shown by MATs tests, as epinephrine and norepinephrine affected its surface polarity. Flow cytometry studies revealed that epinephrine and norepinephrine are unable to induce major changes of bacterial surface properties and membrane integrity. Exposure of sebocytes to control or catecholamine-treated bacteria showed epinephrine and norepinephrine to have no effect on the cytotoxic or inflammatory potential of either C. acnes strains but to stimulate their effect on sebocyte lipid synthesis. Uriage thermal spring water was previously shown to inhibit biofilm production by C. acnes. We thus tested its effect after exposure of the bacteria to epinephrine and norepinephrine. The effect of the thermal water on the response of C. acnes to catecholamines depended on the surface on which the biofilm was grown. Finally, an in-silico study revealed the presence of a protein in the genome of C. acnes that shows homology with the catecholamine receptor of Escherichia coli and eukaryotes. This study suggests that C. acnes may play a role as a relay between stress mediators (catecholamines) and acne.

Refractory Anaphylaxis: Data From the European Anaphylaxis Registry.

Abstract: Refractory anaphylaxis (unresponsive to treatment with at least two doses of minimum 300 μg adrenaline) is a rare and often fatal hypersensitivity reaction. Comprehensive data on its definition, prevalence, and risk factors are missing. Using the data from the European Anaphylaxis Registry (11,596 cases in total) we identified refractory anaphylaxis cases (n = 42) and analyzed these in comparison to a control group of severe anaphylaxis cases (n = 4,820). The data show that drugs more frequently elicited refractory anaphylaxis (50% of cases, p < 0.0001) compared to other severe anaphylaxis cases (19.7%). Cases elicited by insects (n = 8) were more often due to bees than wasps in refractory cases (62.5 vs. 19.4%, p = 0.009). The refractory cases occurred mostly in a perioperative setting (45.2 vs. 9.05, p < 0.0001). Intramuscular adrenaline (as a first line therapy) was administered in 16.7% of refractory cases, whereas in 83.3% of cases it was applied intravenously (significantly more often than in severe anaphylaxis cases: 12.3%, p < 0.0001). Second line treatment options (e.g., vasopression with dopamine, methylene blue, glucagon) were not used at all for the treatment of refractory cases. The mortality rate in refractory anaphylaxis was significantly higher (26.2%) than in severe cases (0.353%, p < 0.0001). Refractory anaphylaxis is associated with drug-induced anaphylaxis in particular if allergens are given intravenously. Although physicians frequently use adrenaline in cases of perioperative anaphylaxis, not all patients are responding to treatment. Whether a delay in recognition of anaphylaxis is responsible for the refractory case or whether these cases are due to an overflow with mast cell activating substances-requires further studies. Reasons for the low use of second-line medication (i.e., methylene blue or dopamine) in refractory cases are unknown, but their use might improve the outcome of severe refractory anaphylaxis cases.

Use of epinephrine in emergency department depends on anaphylaxis severity in children

Abstract: Despite multiple recommendations, intramuscular epinephrine is poorly prescribed in emergency department receiving pediatric anaphylaxis. To evaluate the role of severity symptoms on this use, we included all admissions for a diagnosis linked to possible allergy in the two pediatric emergency departments of our institution between January 2010 and December 2015. Selection and analysis were restricted to children under 18 years fulfilling Sampson’s criteria for anaphylaxis. We retrospectively ranked these admissions with the Ring and Messmer anaphylaxis severity score and compared the use of epinephrine according to this classification. Among 422,483 admissions, 204 (0.05%) fulfilled the anaphylaxis criteria (170 (83.3%) grade II anaphylaxis, and 34 (16.7%) grade III; mean age 7.9 years). Previous allergy, anaphylaxis, and asthma were found in respectively 60.8%, 36.8%, and 35.1%. Food allergy was the main suspected causal trigger. Epinephrine was used in 32.7% (n = 65/199), before admission (11.4% (n = 23/201)) or in the emergency department (22.2% (n = 45/202)). Epinephrine was more frequently prescribed in grade III than in grade II anaphylaxis (84.8% vs 22.3%, p < 0.001; OR = 19.05 [7.05–54.10]). Upon discharge, epinephrine auto-injectors prescription and allergy referral were rare (31.7% and 44.2%). Conclusion: Pediatricians intuitively adapt their epinephrine use to the severity of the anaphylaxis and contribute to epinephrine underuse in pediatric anaphylaxis.

Time to epinephrine treatment is associated with the risk of mortality in children who achieve sustained ROSC after traumatic out-of-hospital cardiac arrest

Abstract: The benefits of early epinephrine administration in pediatric with nontraumatic out-of-hospital cardiac arrest (OHCA) have been reported; however, the effects in pediatric cases of traumatic OHCA are unclear. Since the volume-related pharmacokinetics of early epinephrine may differ obviously with and without hemorrhagic shock (HS), beneficial or harmful effects of nonselective epinephrine stimulation (alpha and beta agonists) may also be enhanced with early administration. In this study, we aimed to analyze the therapeutic effect of early epinephrine administration in pediatric cases of HS and non-HS traumatic OHCA. This was a multicenter retrospective study (2003–2014). Children (aged ≤ 19 years) who experienced traumatic OHCA and were administered epinephrine for resuscitation were included. Children were classified into the HS (blood loss > 30% of total body fluid) and non-HS groups. The demographics, outcomes, postresuscitation hemodynamics (the first hour) after the sustained return of spontaneous circulation (ROSC), and survival durations were analyzed and correlated with the time to epinephrine administration (early 30 min) in the HS and non-HS groups. Cox regression analysis was used to adjust for risk factors of mortality. A total of 509 children were included. Most of them (n = 348, 68.4%) had HS OHCA. Early epinephrine administration was implemented in 131 (25.7%) children. In both the HS and non-HS groups, early epinephrine administration was associated with achieving sustained ROSC (both p < 0.05) but was not related to survival or good neurological outcomes (without adjusting for confounding factors). However, early epinephrine administration in the HS group increased cardiac output but induced metabolic acidosis and decreased urine output during the initial postresuscitation period (all p < 0.05). After adjusting for confounding factors, early epinephrine administration was a risk factor of mortality in the HS group (HR 4.52, 95% CI 2.73–15.91). Early epinephrine was significantly associated with achieving sustained ROSC in pediatric cases of HS and non-HS traumatic OHCA. For children with HS, early epinephrine administration was associated with both beneficial (increased cardiac output) and harmful effects (decreased urine output and metabolic acidosis) during the postresuscitation period. More importantly, early epinephrine was a risk factor associated with mortality in the HS group.

Underuse of Epinephrine for Pediatric Anaphylaxis Victims in the Emergency Department: A Population-based Study.

Abstract: PURPOSE Epinephrine is a key drug for treating anaphylaxis; however, its underuse is still a significant issue worldwide. The objective of this study was to compare epinephrine use between pediatric and adult patients who were treated with anaphylaxis in the emergency department (ED). METHODS The data were retrieved from the National Sample Cohort of South Korea, which contains claim data from the National Health Insurance Service. We included patients who visited the ED with a discharge code of anaphylaxis between 2004 and 2013. We assessed prescription information of epinephrine, antihistamine and systemic steroid, previous medical history and discharge disposition from the ED. The study population was categorized based on age at the visit. RESULTS A total of 175 pediatric and 1,605 adult patients with anaphylaxis were identified. Only 42 (24%) of the pediatric patients were treated with epinephrine, while 592 (36.9%) of the adult patients were treated with epinephrine (P = 0.001). Furthermore, the pediatric patients were less likely to be treated with systemic steroid than the adult patients (6.9% vs. 12.3%, P = 0.047). The odds ratios for the administration of epinephrine relative to the baseline in the 19-65 age group were 0.34 (95% confidence interval [CI], 0.15-0.67), 0.56 (95% CI, 0.28-1.03) and 0.79 (95% CI, 0.45-1.33) in the < 7, 7-12 and 13-18 age groups, respectively. CONCLUSIONS The pediatric patients with anaphylaxis experienced a lower rate of epinephrine injection use than the adult patients and the injection use decreased as age decreased.

Study of the Effects of Epinephrine on Cerebral Oxygenation and Metabolism During Cardiac Arrest and Resuscitation by Hyperspectral Near-Infrared Spectroscopy.

Abstract: OBJECTIVES Epinephrine is routinely administered to sudden cardiac arrest patients during resuscitation, but the neurologic effects on patients treated with epinephrine are not well understood. This study aims to assess the cerebral oxygenation and metabolism during ventricular fibrillation cardiac arrest, cardiopulmonary resuscitation, and epinephrine administration. DESIGN To investigate the effects of equal dosages of IV epinephrine administrated following sudden cardiac arrest as a continuous infusion or successive boluses during cardiopulmonary resuscitation, we monitored cerebral oxygenation and metabolism using hyperspectral near-infrared spectroscopy. SETTINGS A randomized laboratory animal study. SUBJECTS Nine healthy pigs. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Our study showed that although continuous epinephrine administration had no significant impact on overall cerebral hemodynamics, epinephrine boluses transiently improved cerebral oxygenation (oxygenated hemoglobin) and metabolism (cytochrome c oxidase) by 15% ± 6.7% and 49% ± 18%, respectively (p < 0.05) compared with the baseline (untreated) ventricular fibrillation. Our results suggest that the effects of epinephrine diminish with successive boluses as the impact of the third bolus on brain oxygen metabolism was 24.6% ± 3.8% less than that of the first two boluses. CONCLUSIONS Epinephrine administration by bolus resulted in transient improvements in cerebral oxygenation and metabolism, whereas continuous epinephrine infusion did not, compared with placebo. Future studies are needed to evaluate and optimize the use of epinephrine in cardiac arrest resuscitation, particularly the dose, timing, and mode of administration.

Intraoperative dexmedetomidine attenuates stress responses in patients undergoing major spine surgery.

Abstract: BACKGROUND Surgical stress induces stress hormone release and sympathetic hyperactivation, resulting in hemodynamic instability. Dexmedetomidine has sympatholytic and hemodynamic stabilizing effects. We investigated whether dexmedetomidine could attenuate stress responses in major spine surgery. METHODS In this prospective randomized study, 52 patients undergoing spine fusion surgery were randomized to placebo (N.=26) or to dexmedetomidine (N.=26) groups. Dexmedetomidine at a rate of 0.4 μg/kg/h or saline was infused, starting immediately after anesthetic induction and continuing until the end of surgery. Anesthesia was performed using desflurane and remifentanil in both groups. Serum levels of cortisol, epinephrine, norepinephrine, and interleukin-6 were assessed before surgery (T1), at the surgical incision (T2), at the bone procedure (T3), and one hour after surgery (T4). The hemodynamic variables and the autonomic nervous system balance evaluated with heart rate variability were assessed at the same time points. RESULTS Epinephrine and norepinephrine levels were higher over time in the control rather than in the dexmedetomidine group (P=0.001 and <0.001, respectively). The changes in cortisol, interleukin-6, and hemodynamics were similar between the groups. In the heart rate variability analysis, high-frequency decreased and low-frequency and low-frequency/high-frequency ratio increased during surgery in the control group, whereas they were maintained at the baseline level in the dexmedetomidine group. The changes in high-frequency, low-frequency, and the low-frequency/high-frequency ratio over time differed between the groups (P=0.009, 0.024, and 0.011, respectively). CONCLUSIONS Intraoperative dexmedetomidine administration reduced stress hormone release and maintained the balance of the autonomic nervous system. Dexmedetomidine could attenuate surgical stress response without untoward hemodynamic adverse events.

Pharmacokinetic effects of endotracheal, intraosseous, and intravenous epinephrine in a swine model of traumatic cardiac arrest.

Abstract: Introduction Limited prospective data exist regarding epinephrine's controversial role in managing traumatic cardiac arrest (TCA). This study compared the maximum concentration (Cmax), time to maximum concentration (Tmax), plasma concentration over time, return of spontaneous circulation (ROSC), time to ROSC, and odds of ROSC of epinephrine administered by the endotracheal (ETT), intraosseous (IO), and intravenous (IV) routes in a swine TCA model. Methods Forty-nine Yorkshire-cross swine were assigned to seven groups: ETT, tibial IO (TIO), sternal IO (SIO), humeral IO (HIO), IV, CPR with defibrillation (CPRD), and CPR only. Swine were exsanguinated 31% of their blood volume and cardiac arrest induced. Chest compressions began 2 min post-arrest. At 4 min post-arrest, 1 mg epinephrine was administered, and blood specimens collected over 4 min. Resuscitation continued until ROSC or 30 min elapsed. Results The Cmax of IV epinephrine was significantly higher than the TIO group (P = 0.049). No other differences in Cmax, Tmax, ROSC, and time to ROSC existed between the epinephrine groups (P > 0.05). Epinephrine levels were detectable in two of seven ETT swine. No significant difference in ROSC existed between the epinephrine groups and CPRD group (P > 0.05). Significant differences in ROSC existed between all groups and the CPR only group (P Conclusions The pharmacokinetics of IV, HIO, and SIO epinephrine were comparable. Endotracheal epinephrine absorption was highly variable and unreliable compared to IV and IO epinephrine. Epinephrine appeared to have a lesser role than volume replacement in resuscitating TCA.

Epinephrine increases malignancy of breast cancer through p38 MAPK signaling pathway in depressive disorders.

Abstract: Objective To uncover the possible mechanism and the effects of epinephrine on tumor growth in depression. Materials and methods A chronic mild stress (CMS) model was employed to test the change of serum epinephrine levels in mice with depression. Tumor tissues and cell lines were analyzed to identify the molecular and cellular events influenced by depression in vitro. Results The level of epinephrine was up-regulated in CMS mice serum. We found that β-adrenergic receptors (β-ARs) were expressed on MCF-7 and MDA-MB-231 breast cancer cells and that epinephrine enhanced the proliferation, migration, and invasion of breast cancer cells. Treatment of epinephrine increased the phosphorylation of p38 MAPK in cells and enhanced the growth of tumor in vivo. These two effects were significantly attenuated by propranolol (a β-adrenergic receptor antagonist). Conclusions These findings suggest that activation of epinephrine-induced p38 MAPK signaling pathway enhances the malignancy of breast cancer in depressive disorders. More effective psychological intervention might improve prognosis of cancer patients.

Phentolamine Reverses Epinephrine-Enhanced Skin Antinociception of Dibucaine in Rats.

Abstract: BACKGROUND:The objective of the experiment was to assess the antinociceptive effect of dibucaine, bupivacaine, and epinephrine. To assess the mechanism of action of the interaction between dibucaine and epinephrine, phentolamine, a nonselective α-adrenergic antagonist, was added to the mixture.METHO

The Association of Hospital Rate of Delayed Epinephrine Administration With Survival to Discharge for Pediatric Nonshockable In-Hospital Cardiac Arrest.

Abstract: Objectives To evaluate the variation of hospital rates of delayed epinephrine administration in pediatric patients with nonshockable in-hospital cardiac arrest, and the association of those rates with event, 24-hour, and overall survival to hospital discharge. Design A retrospective evaluation was performed. Delayed epinephrine was defined as greater than 5 minutes between the time the need for chest compressions was identified and epinephrine was administered. The main outcome was the association of hospital rate of delayed epinephrine administration with survival to hospital discharge. Secondary outcomes were event and 24-hour survival. Evaluation used hierarchical logistic regression and included 13 patient/event-level and seven hospital-level factors. Setting Hospitals with greater than 6 months data in the American Heart Association's Get With the Guidelines-Resuscitation registry (2000-2016) and greater than or equal to five total pediatric cardiac arrests with nonshockable rhythm. Patients Children less than 18 years old with index nonshockable in-hospital cardiac arrest treated with greater than or equal to one epinephrine dose. Interventions None. Measurements and main results One-thousand four-hundred sixty-two patients at 69 hospitals were included: 218 patients (14.9%) had epinephrine delay rates ranging from 0% to 80% of events (median, 15.6%; interquartile range, 7-25%). The median and interquartile range of hospital level delay was 16% (7-25%). Patient/event-level predictors of delayed epinephrine were asystole (odds ratio, 1.54 [95% CI, 1.10-2.16]) and insertion of an endotracheal tube (odds ratio, 1.86 [95% CI, 1.27-2.73]). Hospital size less than 200 compared with greater than or equal to 500 beds (odds ratio, 3.07 [95% CI, 1.22-7.73]) and ICU location (odds ratio, 0.51 [95% CI, 0.36-0.74]) were associated with epinephrine delay rates. After adjustment, increasing quartiles of epinephrine delay were associated with lower patient and hospital-level return of spontaneous circulation (p = 0.019, p = 0.006) and 24-hour survival (p = 0.018, p = 0.002) respectively, but not survival to discharge (p = 0.20, p = 0.24). Conclusions Delayed epinephrine administration following pediatric nonshockable in-hospital cardiac arrest varies significantly between hospitals. Hospitals with higher rates of delayed epinephrine administration had worse patient- and hospital-level outcomes after adjusting for multiple patient- and hospital-level factors. Delayed epinephrine administration may directly contribute to increased mortality risk and/or may be a marker of unmeasured elements of hospital resuscitation performance.

Absence of gut microbial colonization attenuates the sympathoadrenal response to hypoglycemic stress in mice: implications for human neonates

Abstract: Gut microbiota plays an important role during early development via bidirectional gut–brain signaling. Catecholamines provide a survival advantage allowing adaptation to common postnatal stressors. We aimed to explore the potential link between gut microbiota/gut-derived metabolites and sympathoadrenal stress responsivity. The effect of insulin-induced hypoglycemia was compared in mice with (control, adapted control) and without microbiome (germ-free, GF). Counter-regulatory hormones were analyzed in urine and plasma. Adrenal gene expression levels were evaluated and correlated to cecal short chain fatty acids (SCFA) content. There was a significant association between absent microbiota/SCFA and epinephrine levels at baseline and after stress. Corticosterone (hypothalamic-pituitary-adrenal axis) and glucagon release (parasympathetic signaling) were similar in all groups. Hypoglycemia-induced c-Fos (marker of trans-synaptic neuronal activation) in both conditions. Delayed increases in adrenal tyrosine hydroxylase and neuropeptide Y messenger RNA were observed in GF mice. Transcriptome analysis provided insight into underlying mechanisms for attenuated epinephrine production and release. Lack of microbiome selectively impaired adrenal catecholamine responses to hypoglycemia. We speculate that absent/delayed acquisition of flora (e.g., after antibiotic exposure) may compromise sympathoadrenal stress responsivity. Conversely, controlled manipulation of the intestinal microflora may provide a novel therapeutic opportunity to improve survival and overall health in preterm neonates.

The First Hormone: Adrenaline.

Abstract: It is not often that three misconceptions are associated with one molecule for more than a century. This is the case with adrenaline. The aim here is to clarify that adrenaline was the first hormone, with the discovery of its activity and chemical purification being prior to secretin. Adrenaline is the correct name given by Jōkichi Takamine, epinephrine being its inactive benzoyl derivative.

Combination era, using combined vasopressors showed benefits in treating septic shock patients: a network meta-analysis of randomized controlled trials

Abstract: Background: Septic shock is one of the major healthcare problems, affecting millions of people around the world every year. The object of this study is to find the best kind of regimen of vasopressors treatment in septic shock. Methods: The PubMed, and the Web of Science were used to find the included studies. Stata 15.1 was performed to this systemic review and network meta-analysis. Results: After searching and screening the articles, finally we included articles about 31 randomized controlled trials (RCTs), 11 arms (dopamine, dopexamine, epinephrine, norepinephrine, norepinephrine + dobutamine, norepinephrine + dopexamine, norepinephrine + epinephrine, norepinephrine + vasopressin, phenylephrine, terlipressin, vasopressin) and total 5,928 patients with septic shock. Compared with dopamine, the regimens (epinephrine, norepinephrine, norepinephrine + dobutamine, and vasopressin) have significantly lower 28-day mortality. Ranking the regimens in the order of estimated probabilities of each treatment by using the network meta-analysis for 28-day mortality, the result showed that norepinephrine + dopexamine was the best one (57.3%), followed by norepinephrine + epinephrine (14.8%), norepinephrine + dobutamine (10.9%), dopexamine (11.2%), terlipressin (9.8%), norepinephrine + vasopressin (2.4%), phenylephrine (1.2%), epinephrine (1.0%), vasopressin (0.5%), norepinephrine (0.0%), and dopamine (0.0%). In addition, for the results of arrhythmia and increased heart rate, the combination regimens groups did not showed inferiority to other single regimen groups. Conclusions: Single dopamine had significantly higher 28d mortality. Combination regimens of vasopressors accounted for the best three therapeutic regimens. In treating patients with septic shock, using combining regimens probably gets more benefits.

Association of Prehospital Epinephrine Administration With Survival Among Patients With Traumatic Cardiac Arrest Caused By Traffic Collisions

Abstract: For traumatic cardiac arrest (TCA), the effect of prehospital epinephrine administration was unclear The aim of this study was to evaluate the relationship between prehospital epinephrine administration and survival in patients with TCA caused by traffic collisions We conducted a nationwide, prospective, population-based observational study involving patients who experienced out-of-hospital cardiac arrest (OHCA) by using the All-Japan Utstein Registry Blunt trauma patients with TCA who received prehospital epinephrine were compared with those who did not receive prehospital epinephrine The primary outcome was 1-month survival of patients The secondary outcome was prehospital return of spontaneous circulation (ROSC) A total of 5,204 patients with TCA were analyzed Of those, 758 patients (146%) received prehospital epinephrine (Epinephrine group), whereas the remaining 4,446 patients (854%) did not receive prehospital epinephrine (No epinephrine group) Eleven (15%) and 41 (09%) patients in the Epinephrine and No epinephrine groups, respectively, survived for 1 month In addition, 74 (98%) and 40 (09%) patients achieved prehospital ROSC in the Epinephrine and No epinephrine groups, respectively In multivariable logistic regression models, prehospital epinephrine administration was not associated with 1-month survival (odds ratio [OR] 1495, 95% confidence interval [CI] 0758 to 2946) and was associated with prehospital ROSC (OR 3784, 95% CI 2102 to 6812) A propensity score-matched analysis showed similar results for 1-month survival (OR 2363, 95% CI 0606 to 9,223) and prehospital ROSC (OR 6870, 95% CI 3326 to 14192) Prehospital epinephrine administration in patients with TCA was not associated with 1-month survival, but was beneficial in regard to prehospital ROSC

Ivabradine reduces baseline and stress-induced increase of heart rate and blood pressure and modulates neuroendocrine stress response in rats depending on stressor intensity.

Abstract: Ivabradine, a selective inhibitor of the sinoatrial pacemaker, is used in clinical practice to reduce heart rate. However, its potential effect on the neuroendocrine stress response has not been investigated. Therefore, we determined the effect of administering ivabradine to rats on cardiovascular parameters and plasma levels of epinephrine, norepinephrine, and corticosterone. Ivabradine was administered intraperitoneally 30 min before exposing animals to either handling, restraint, or immobilization stress. Heart rate and blood pressure were monitored telemetrically. Blood samples were collected before, during, and after stressor exposure to determine the extent of the neuroendocrine stress response as reflected by plasma epinephrine, norepinephrine, and corticosterone levels. In animals pretreated with ivabradine, significantly lower values of heart rate and blood pressure were found during both the baseline period and during exposure to stressors, as well as during the rest period following stressor exposure. Ivabradine also significantly reduced handling-induced epinephrine and norepinephrine release into the bloodstream. However, ivabradine significantly potentiated restraint- and immobilization-induced increases of plasma epinephrine levels, whereas stress-induced changes in plasma norepinephrine and corticosterone levels were ambiguous. Our data shows that ivabradine significantly reduces blood pressure in rats during both baseline and stressful conditions, and also affects the neuroendocrine stress response. These findings show that viscerosensory signaling from the cardiovascular system may significantly modulate the neuroendocrine stress response.

A systematic review of epinephrine stability and sterility with storage in a syringe.

Abstract: Epinephrine is a lifesaving medication in the treatment of anaphylaxis. Epinephrine auto-injectors are the preferred method of epinephrine administration, but are not universally available or affordable. Little is known about the effects on epinephrine when it is drawn up in advance and stored as prefilled syringes. To study the stability and sterility of epinephrine when stored in syringes. We searched Embase, Medline, and Web of Science in June 2016 for all studies of epinephrine stored in syringes in concentrations between 0.1 and 1 mg/mL that measured epinephrine stability and/or sterility over time, regardless of date published or language. Three studies were included, one testing two concentrations of epinephrine. Only one study tested epinephrine 1 mg/mL, the concentration clinically relevant for intramuscular use during anaphylaxis. Neither this study nor the one study testing 0.7 mg/mL epinephrine found significant degradation after 56 and 90 days, respectively. One of the two studies testing epinephrine at a concentration of 0.1 mg/mL found significant degradation by 14 days; the other found no degradation up to 168 days. Two studies tested for bacterial growth, with none detected after 28 and 90 days, respectively. One study tested for fungal growth, with none detected after 90 days. Limited evidence suggests that syringes filled with 1 mg/mL epinephrine are stable and sterile for 90 days. More research is needed testing the duration of stability and sterility of prefilled syringes with the 1 mg/mL concentration most commonly used in anaphylaxis, testing more extensively in different storage conditions and across a wider range of marketed syringe brands.

Carrying rates of epinephrine devices in children with food-induced anaphylaxis

Abstract: Background Carrying epinephrine can save lives in patients with anaphylaxis. The feature of epinephrine in prefilled syringe that commonly prescribed in Thailand may influence the willingness to carry. However, the rates of carrying prefilled syringe epinephrine are unknown in children with history of food-induced anaphylaxis. Objective To determine the rate of epinephrine carrying in children with history of food-induced anaphylaxis and factors influencing the decision to use the devices. Methods A cross-sectional study was conducted by performing the structured interview in the parent(s) who were the main caregiver of the children with history of food-induced anaphylaxis. Results The parents of 99 children (male, 50.5%) were interviewed. The median age of the child was 11 years old (range, 9 months to 18 years). Rate of carrying epinephrine was 84.7% (always 57.6%, some occasions 27.2%). The most common reason for not carrying was the thoughts that the children could avoid the food allergens. The first-aid facility at school was available in 48.3%. Rate of carrying epinephrine tended to be lesser in children attend the schools without first aid facility (p = 0.053). Forty-one patients had relapsing episodes, 34 (82.9%) had epinephrine carried, and 20 (58.8%) injected the epinephrine. The most common reason for not using epinephrine despite carrying was that they were afraid of getting injection (28.5%). Conclusion Most children with history of food-induced anaphylaxis carried epinephrine, but only half used it at the episodes. Interventions to promote epinephrine-carrying and injection training are needed in our setting.

Pathophysiology of Diabetes

Abstract: The pathophysiology of diabetes is related to the levels of insulin within the body, and the body’s ability to utilize insulin. There is a total lack of insulin in type 1 diabetes, while in type 2 diabetes, the peripheral tissues resist the effects of insulin. Normally, the pancreatic beta cells release insulin due to increased blood glucose concentrations. The brain in order for normal functions to occur continually requires glucose. Hypoglycemia, or low plasma glucose levels, is usually caused by drugs used in the treatment of diabetes, including insulin and oral antihyperglycemics. The pathophysiology of diabetes involves plasm concentrations of glucose signaling the central nervous system to mobilize energy reserves. It is based on cerebral blood flow and tissue integrity, arterial plasma glucose, the speed that plasma glucose concentrations fall, and other available metabolic fuels. Low plasma glucose causes a surge in autonomic activity. Diagnosis of hypoglycemia requires verification of low plasma glucose levels. Immediate treatment is the intake of glucose. The responses to hypoglycemia include decreased insulin secretion, increased secretion of glucose counter-regulatory hormones such as glucagon and epinephrine, a greater sympathoadrenal response, related symptoms, and finally, cognitive dysfunction, seizures, or coma. Late hypoglycemia of occult diabetes may develop in some patients with impaired glucose tolerance, or early type 1 or type 2 diabetes. After a high-carbohydrate meal, the patient experiences hypoglycemia.

Efficacy of low-dose nebulized epinephrine as treatment for croup: A randomized, placebo-controlled, double-blind trial

Abstract: Objective Croup treatment usually involves a single dose of systemic dexamethasone combined with nebulized epinephrine. However, the optimal dose of l -epinephrine remains unclear. We examined whether a low dose (0.1 mg/kg) was inferior to the conventional dose (0.5 mg/kg) of 1:1000 nebulized l -epinephrine in patients with moderate to severe croup. Methods This randomized double-blind clinical non-inferiority trial was conducted in three pediatric emergency departments from May 2015 to October 2017. Children 6 months to 5 years old with moderate to severe croup (Westley scale scores 3–11) were eligible. Subjects were randomly assigned to the conventional dose (0.5 mg/kg: maximum 5 mg) or low dose (0.1 mg/kg; maximum 1 mg) group. All subjects received 0.6 mg/kg dexamethasone. Croup scores and other vital signs were measured before and at 30, 60, 90, and 120 min after nebulized l -epinephrine administration. The primary outcome was the change in croup score after 30 min. Results The final analysis included 84 patients. The groups did not differ significantly in terms of demographic parameters. At 30 min after treatment with nebulized l -epinephrine, the croup scores in both groups were significantly reduced from the baseline values (p Conclusions Low-dose 1:1000 l -epinephrine was not inferior in croup score reduction to the conventional dose in patients with moderate to severe croup. Clinical trial No: NCT01664507 , KCT0002318.