Intravenous Infusion Of Epinephrine Research Articles

Adrenaline intravenous therapy persistence grade I severe allergic reaction: A case report and literature review.

At present, there is still insufficient understanding of the progression from persistent allergic reactions to severe reactions. Adrenaline remains the preferred medication for severe allergic reactions, and intramuscular injection of adrenaline can also be considered for patients with grade I reactions that are difficult to alleviate gastrointestinal symptoms. It is worth further discussing whether it is possible to break the conventional intramuscular injection recommended by the guidelines when the effect of intramuscular injection is not ideal for persistent grade I severe allergic reactions. A young male, 20 years of age, was admitted to emergency department because of repeated rash for 3 days and abdominal pain for 6 hours after taking traditional Chinese medicine. After hormone therapy, the rash continued to recur and secondary gastrointestinal symptoms occurred on the 3th day. Adrenaline intramuscular injection was given to temporarily relieve the rash and abdominal pain, but symptoms still persisted. The patient was diagnosed with persistent severe allergic reaction (grade I). Continuous intravenous infusion of low-dose adrenaline under electrocardiographic monitoring, real-time monitoring of heart rate and blood pressure, and routine treatment with methylprednisolone, diphenhydramine, calcium gluconate, and cetirizine. During this period, adrenaline intramuscular injection is temporarily added when abdominal pain symptoms are obvious. The entire treatment process used a total of 6.8 mg of adrenaline. During the entire period of adrenaline intervention, the patient did not experience any new discomfort, and there were no abnormal fluctuations in heart rate, rhythm, or blood pressure. The symptoms of rash and abdominal pain gradually improved. For patients with persistent grade I severe allergic reactions, intravenous administration of low-dose adrenaline under close vital sign monitoring is safe, feasible, and highly effective in preventing biphasic, persistent, or worsening allergic reactions.

Efficacy of Low Dose Intravenous Epinephrine Infusion in Improving Perioperative Outcomes in Patients Undergoing Transurethral Resection of Prostate: A Prospective Parallel Arm Double-Blind Randomized Control Trial

ObjectiveTo determine the efficacy of intraoperative low-dose intravenous epinephrine infusion in improving intraoperative bleeding and perioperative outcomes of TURP surgery. MethodsThis was a double-blinded, randomized control trial in which all patients undergoing bipolar TURP were included. Patients with uncontrolled hypertension, cardiac disease, and on anticoagulants were excluded. The study group received intravenous epinephrine, whereas the control group received normal saline at the same rate (0.05 μg/kg/min) throughout the procedure. Intraoperative blood loss was the primary outcome. The secondary outcomes were incidence of intraoperative hypotension (due to spinal anesthesia (SA)), resection time, indwelling catheter time, and length of hospitalization (LOH). ResultsThirty-six patients were included in each group. Demographic and clinical profiles were comparable with an overall median prostate size of 41 (34-52) gram in both groups. The primary objective, mean intraoperative blood loss in the study group was lower than the control group but statistically insignificant (67.91+/-18.7 ml vs 75.14+/-17.1 ml; p=0.086). Incidence of intraoperative hypotension was significantly lower in the study group (8.3% vs 33.3%; p= 0.01). Rest of the secondary outcomes, resection time (83 (64-111.5) min vs 86 (68-94.75) min; p=0.97), mean indwelling catheter time (p=0.94), postoperative complications (p=0.73), and LOH (p=0.87) were comparable. ConclusionsIn this first-of-its-kind trial, low-dose epinephrine infusion did not reduce intraoperative blood loss in patients undergoing TURP. However, it significantly reduced intraoperative hypotension, which complicates SA particularly in elderly population.

Cardiac Arrest Caused by Anaphylaxis Refractory to Prompt Management

BackgroundAnaphylaxis is a potentially life-threatening condition that occurs in the emergency department (ED). Although anaphylaxis is rapidly recognized and treated in the hospital compared with that in the community, in some cases, it does not respond to proper management. ObjectiveThe aim of this study is to describe our experience of cases of refractory anaphylaxis leading to cardiac arrest in hospital, to review their characteristics compared with those seen in the community, and to discuss the best management practices for anaphylaxis-induced cardiac arrest with a literature review. MethodsWe reviewed the medical records of patients referred to the ED with possible in-hospital anaphylaxis between January 2017 and May 2021. According to the anaphylaxis protocol, epinephrine, corticosteroid, and antihistamine were administered immediately on-site at our institution before the study period. Refractory anaphylaxis was defined as the development of anaphylaxis-induced cardiac arrest even after following the anaphylaxis protocol. ResultsA total of 246 cases were evaluated for possible anaphylaxis, with 236 cases meeting the criteria for a diagnosis of anaphylaxis. Among them, 178 patients showed the signs and symptoms of shock, and cardiac arrest occurred in 6 patients (2.5%). Of the six patients, three had a return of spontaneous circulation before admission to the ED, while two died due to refractory cardiac arrest despite resuscitation in the ED. Following post-cardiac arrest care, including temperature management, one patient who received extracorporeal cardiopulmonary resuscitation survived neurologically intact. ConclusionWe present our case series to highlight the risk of developing refractory anaphylaxis with subsequent in-hospital cardiac arrest. Patients may progress to cardiac arrest within minutes despite prompt recognition and management. If patients present with potentially fatal symptoms, a more aggressive approach, including intravenous adrenaline infusion, should be taken.

An Estimate of Plasma Volume Changes Following Moderate-High Intensity Running and Cycling Exercise and Adrenaline Infusion.

Introduction: Plasma volume (PV) changes in response to physical activity, possibly as a consequence of adrenergic activation. We estimated changes in PV in response to common exercise modalities; cycling and running as well as adrenaline infusion and control at rest. Methods: On separate days, forty circulatory healthy subjects [aged 60 years (range: 42–75)] with knee osteoarthritis underwent moderate-high intensity cycling, running, and intravenous adrenaline infusion to mimic the circulatory response to exercise. Blood samples were obtained from peripheral veins taken at several pre-defined time points before, during, and after the interventions. PV changes were estimated using venous hemoglobin and the derived hematocrit. The temporal associations between PV and selected biomarkers were explored. Results: Changes in PV were observed during all four interventions, and the response to cycling and running was similar. Compared to rest, PV decreased by -14.3% (95% CI: -10.0 to -18.7) after cycling, -13.9% (95% CI: -10.9 to -17.0) after running, and -7.8% (95% CI: -4.2 to -11.5) after adrenaline infusion. Conclusion: PV decreased in response to moderate-high intensity running and cycling. Adrenaline infusion mimicked the PV change observed during exercise, suggesting a separate influence of autonomic control on blood volume homeostasis. In perspective, a temporal association between PV and biomarker dynamics suggests that consideration of PV changes could be relevant when reporting plasma/serum constituents measured during exercise, but more research is needed to confirm this.

Updating the CoFAR Grading Scale for Systemic Allergic Reactions in Food Allergy

Immunotherapy is promising as an efficacious treatment for food allergy. Other food allergy treatments are also under development. However, adverse allergic events during treatment, as well as during oral food challenges, are common and reporting is not standardized. A more nuanced grading scale is needed to create a comprehensive and universal system to categorize adverse events and their severity for food allergy clinical trials. Starting with the 2012 Consortium for Food Allergy Research (CoFAR) Grading Scale and the World Allergy Organization Grading System, we developed the CoFAR Grading Scale for Systemic Allergic Reactions, Version 3.0, in collaboration with industry partners with expert opinion. The revised CoFAR Grading Scale for Systemic Allergic Reactions has 5 levels of increasing severity, ranging from generalized urticaria, localized angioedema, rhinitis, and abdominal pain (grade 1) to death (grade 5). Systemic reactions are further categorized within each grade by relevant organ system. Mild, single-system reactions are differentiated from mild, multisystem reactions. Lower respiratory tract symptoms are graded on the basis of response to therapy; those that are refractory to standard treatment (eg, requiring >3 doses of intramuscular epinephrine, continuous intravenous epinephrine infusion, and continuous albuterol nebulization) and respiratory compromise requiring mechanical ventilation are classified as grade 4, life-threatening reactions. Universal and consistent use of the revised CoFARGrading Scale beyond the CoFAR centers would allow for better data aggregation and safety comparisons in clinicaltrials for food allergy.

Comparison of the efficacy of continuous intravenous infusion versus intramuscular injection of epinephrine for initial anaphylaxis treatment.

AimContinuous intravenous (CIV) infusion of epinephrine for the treatment of anaphylaxis may be required if symptoms do not improve after intramuscular (IM) injection. As CIV infusion permits precise dose adjustment, we compared treatment course and adverse events following CIV infusion and IM injection of epinephrine for the management of anaphylaxis.MethodsMedical records of patients, who were treated for anaphylaxis with epinephrine, were 18 years or older, and were admitted to our department from April 2005 to March 2016, were retrospectively reviewed. The cases were categorized as CIV infusion or IM injection, and treatment course and outcomes were compared between the two groups.ResultsOf the 142 eligible cases, there were 78 in the CIV infusion group and 64 in the IM injection group. The CIV infusion group had lower systolic blood pressure, more respiratory symptoms, and higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, but required a lower total dose of epinephrine, had fewer adverse events after epinephrine administration, and showed lower incidence of biphasic reactions. In addition, compared with the IM injection group, time to administration of epinephrine was significantly longer (P < 0.001), but time to resolution of symptoms, both from contact and epinephrine administration, was significantly shorter (P < 0.01 and P = 0.03, respectively).ConclusionContinuous intravenous infusion of epinephrine for the treatment of anaphylaxis may be safe, has fewer adverse events, improves symptoms, and is relatively easy to administer under ready conditions. CIV infusion of epinephrine may also reduce the incidence of biphasic reactions.

Early Resuscitation in Paediatric Sepsis Using Inotropes – A Randomised Controlled Pilot Study in the Emergency Department (RESPOND ED): Study Protocol and Analysis Plan

Introduction: Septic shock in children still carries substantial mortality and morbidity. While resuscitation with 40–60 mL/kg intravenous fluid boluses remains a cornerstone of initial resuscitation, an increasing body of evidence indicates potential for harm related to high volume fluid administration. We hypothesize that a protocol on early use of inotropes in children with septic shock is feasible and will lead to less fluid bolus use compared to standard fluid resuscitation. Here, we describe the protocol of the Early Resuscitation in Paediatric Sepsis Using Inotropes – A Randomised Controlled Pilot Study in the Emergency Department (RESPOND ED).Methods and analysis: The RESPOND ED study is an open label randomised controlled, two arm, multicentre pilot study conducted at four specialised paediatric Emergency Departments. Forty children aged between 28 days and 18 years treated for presumed septic shock will be randomized in a 1:1 ratio to early inotropes vs. standard fluid resuscitation. Early inotrope treatment is defined as the commencement of a continuous intravenous adrenaline infusion after 20 mL/kg fluid bolus resuscitation. Standard fluid resuscitation is defined as delivery of 40 to 60 mL/kg fluid bolus resuscitation prior to commencement of inotropes. In addition to feasibility outcomes, survival free of organ dysfunction censored at 28 days will be assessed as the main clinical outcome. The study cohort will be followed up at 28 days, and at 6 months post enrolment to assess quality of life and functional status. Biobanking nested in the study cohort will be performed to enable ancillary biomarker studies.Ethics and dissemination: The trial has ethical clearance (Children's Health Queensland, Brisbane, HREC/18/QCHQ/49168) and is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12619000828123). Enrolment commenced on July 21st, 2019. The primary manuscript will be submitted for publication in a peer-reviewed journal.Trial Registration: Australian and New Zealand Clinical Trials Registry, ACTRN12619000828123.

The effects of moderate alterations in adrenergic activity on acute appetite regulation in obese women: A randomised crossover trial.

Background:Previous evidence has demonstrated that serum leptin is correlated with appetite in combination with, but not without, modest exercise.Aim:The present experiments investigated the effects of exogenous adrenaline and α/β adrenoceptor blockade in combination with moderate exercise on serum leptin concentrations, appetite/satiety sensations and subsequent food intake in obese women.Methods:A total of 10 obese women ((mean ± SEM), age: 50 (1.9) years, body mass index 36 (4.1) kg/m2, waist 104.8 (4.1) cm) participated in two separate, double-blind randomised experimental trials. Experiment 1: moderate exercise after α/β adrenergic blocker (labetalol, 100 mg orally) versus moderate exercise plus placebo; experiment 2: adrenaline infusion for 20 minutes versus saline infusion. Appetite/satiety and biochemistry were measured at baseline, pre- and immediately post-intervention, then 1 hour post-intervention (i.e., before dinner). Food intake was assessed via ad libitum buffet-style dinner.Results:No differences were found in appetite/satiety, subsequent food intake or serum leptin in any of the studies (experiment 1 or experiment 2). In experiment 1, blood glucose was higher (p < 0.01) and plasma free fatty acids lower (p = 0.04) versus placebo. In experiment 2, plasma free fatty acids (p < 0.05) increased after adrenaline versus saline infusion.Conclusions:Neither inhibition of exercise-induced adrenergic activity by combined α/β adrenergic blockade nor moderate increases in adrenergic activity induced by intravenous adrenaline infusion affected acute appetite regulation.

Acute Severe Anaphylaxis in Nepali Patients with Neurotoxic Snakebite Envenoming Treated with the VINS Polyvalent Antivenom.

Diagnosing and treating acute severe and recurrent antivenom-related anaphylaxis (ARA) is challenging and reported experience is limited. Herein, we describe our experience of severe ARA in patients with neurotoxic snakebite envenoming in Nepal. Patients were enrolled in a randomised, double-blind trial of high vs. low dose antivenom, given by intravenous (IV) push, followed by infusion. Training in ARA management emphasised stopping antivenom and giving intramuscular (IM) adrenaline, IV hydrocortisone, and IV chlorphenamine at the first sign/s of ARA. Later, IV adrenaline infusion (IVAI) was introduced for patients with antecedent ARA requiring additional antivenom infusions. Preantivenom subcutaneous adrenaline (SCAd) was introduced in the second study year (2012). Of 155 envenomed patients who received ≥ 1 antivenom dose, 13 (8.4%), three children (aged 5−11 years) and 10 adults (18−52 years), developed clinical features consistent with severe ARA, including six with overlapping signs of severe envenoming. Four and nine patients received low and high dose antivenom, respectively, and six had received SCAd. Principal signs of severe ARA were dyspnoea alone (n=5 patients), dyspnoea with wheezing (n=3), hypotension (n=3), shock (n=3), restlessness (n=3), respiratory/cardiorespiratory arrest (n=7), and early (n=1) and late laryngeal oedema (n=1); rash was associated with severe ARA in 10 patients. Four patients were given IVAI. Of the 8 (5.1%) deaths, three occurred in transit to hospital. Severe ARA was common and recurrent and had overlapping signs with severe neurotoxic envenoming. Optimising the management of ARA at different healthy system levels needs more research. This trial is registered with NCT01284855.

Synchronized Pulsatile Flow With Low Systolic Output From Veno-Arterial Extracorporeal Membrane Oxygenation Improves Myocardial Recovery After Experimental Cardiac Arrest in Pigs.

Circulatory failure following cardiac arrest (CA) requires catecholamine support and occasionally veno-arterial extracorporeal membrane oxygenation (vaECMO). VaECMO-generated blood flow is continuous and retrograde, increasing ventricular stroke work. Our aim was to assess the benefit of a device generating a pulsatile vaECMO flow synchronized with the heart rhythm lowering systolic vaECMO output on the left ventricular ejection fraction (LVEF) and pulmonary capillary pressure (Pcap) after CA. This experimental randomized study in pigs compared standard nonpulsatile vaECMO (control) with pulsatile synchronized vaECMO (study) group using a pulsatility-generating device. After sedation and intubation, ventricular fibrillation was induced by pacing. After 10-min ventricular fibrillation, cardiopulmonary resuscitation was performed for 20 min then vaECMO, defibrillation and 0.15 µg/kg/min intravenous epinephrine infusion were initiated. Hemodynamics, Pcap, LVEF by echocardiography and angiography were measured at baseline and every 30 min after the vaECMO start until vaECMO and epinephrine were stopped (at 120 min), and 30 min later. Baseline hemodynamics did not differ between groups; 120 min after vaECMO initiation, LVEF by echocardiography and angiography was significantly higher in the study than control group 55 ± 19% versus 34 ± 13% (P = 0.042), 50 ± 16% versus 33 ± 12% (P = 0.043), respectively. Pcap decreased from baseline by 4.2 ± 8.6 mm Hg in the study group but increased by 5.6 ± 5.9 mm Hg in the control group (P = 0.043). Thirty minutes later, LVEF remained higher in the study group 44 ± 7% versus 26 ± 11% (P = 0.008) while Pcap did not differ. A synchronized pulsatile device decreasing systolic output from vaECMO improved LVEF and Pcap in a pig model of CA and resuscitation.

Low-Dose Epinephrine Infusions and Tranexamic Acid During Lower-Extremity Total Joint Arthroplasty: Commentary on an article by Wei-Nan Zeng, MD, et al.: "Low-Dose Epinephrine Plus Tranexamic Acid Reduces Early Postoperative Blood Loss and Inflammatory Response. A Randomized Controlled Trial".

Low-Dose Epinephrine Infusions and Tranexamic Acid During Lower-Extremity Total Joint Arthroplasty: Commentary on an article by Wei-Nan Zeng, MD, et al.: "Low-Dose Epinephrine Plus Tranexamic Acid Reduces Early Postoperative Blood Loss and Inflammatory Response. A Randomized Controlled Trial".

A confirmed case of sugammadex-induced anaphylaxis in a UK hospital

We report the first published case of confirmed anaphylaxis to sugammadex in a UK hospital. The patient was given a bolus of sugammadex at the end of surgery. Four minutes...

Hypotensive epidural anesthesia in patients with preoperative renal dysfunction presenting for hip arthroplasty

Objective To investigate the benefits and safety of hypotensive epidural anesthesia (HEA) in comparison with normotensive epidural anesthesia in patients with preoperative renal dysfunction presenting for hip arthroplasty. Background HEA is one of the anesthetic techniques used to reduce perioperative blood loss for total hip replacement. The technique includes a combination of an extensive epidural block and an intravenous infusion of low-dose epinephrine (1–5 μg/min) to adjust and control the mean arterial blood pressure together with preserving central venous pressure and cardiac output. Patients and methods Forty adult patients of both sexes undergoing primary unilateral hip arthroplasty, ranging in age from 60 to 74 years, ASA II–III with mild renal dysfunction were divided into two groups: group I received epidural anesthesia with strict preservation of the mean arterial blood pressure (65–90 mmHg) during surgery using vasopressors, fluids, and/or blood transfusions and group II received epidural anesthesia and hypotension was induced by maintaining the mean arterial blood pressure at 55–60 mmHg during the entire surgery. Results The heart rate and the mean arterial blood pressure showed a significant difference between the two groups at 15, 30, 45, 60, and 90 min intraoperatively (P Conclusion HEA is superior to normotensive epidural anesthesia in patients with renal impairment undergoing hip arthroplasty in the form of decreased blood loss and the need for blood infusion, provides a clear surgical field, and leads to an improvement in cement fixation and decreased incidence of postoperative deep vein thrombosis and blood loss, with no evidence of acute kidney injury postoperatively.

Hypotensive Epidural Anesthesia Reduces Blood Loss in Pelvic and Sacral Bone Tumor Resections

Resection of pelvic and sacral tumors can cause severe blood loss, complications, and even postoperative death. Hypotensive epidural anesthesia has been used to mitigate blood loss after elective arthroplasty, but to our knowledge, it has not been studied as an approach that might make resection of pelvic and sacral tumors safer. The purposes of this study were (1) to compare the blood loss and blood product use for patients undergoing pelvic and sacral tumor surgery under standard anesthesia or hypotensive epidural anesthesia; (2) to assess the frequency of end-organ damage with the two techniques; and (3) to compare 90-day mortality between the two techniques. Between 2000 and 2014, 285 major pelvic and sacral resections were performed at one center. A total of 174 (61%) had complete data sets for analysis of blood loss, transfusion use, complications, and mortality at 90 days. Of those, 102 (59%) underwent hypotensive epidural anesthesia, whereas the remainder received standard anesthetic care. The anesthetic approach was determined by the anesthetists in charge of the case with hypotensive epidural anesthesia exclusively performed by one of two subspecialty trained anesthetists as their routine for major pelvic or sacral surgery. The groups were comparable in terms of potential confounding variables such as age, gender, tumor volume, and operation performed. Hypotensive epidural anesthesia was defined as a technique using an extensive epidural block up to T2-3 dermatome, peripherally administered low-concentration intravenous adrenaline infusion, and using unimpeded spontaneous respiration to achieve controlled hypotension, precise rate control of the heart, and enhanced velocity of venous return, all aggregated thus to minimize blood loss during pelvic surgery while preserving vital perfusion. The groups were assessed for perioperative blood loss calculated from pre- and postsurgery hemoglobin and transfusion use as well as postoperative complications, morbidity, and mortality at 90 days. There was less mean blood loss in the hypotensive epidural anesthesia group (1457 mL, SD 1721, 95% confidence interval [CI], 1114-1801 versus 2421 mL, SD 2297, 95% CI, 1877-2965; p = 0.003). Patients in the hypotensive epidural anesthesia group on average received fewer packed red cell transfusions (2.7 units, SD 2.9, 95% CI, 2.1-3.2 versus 3.9 units, SD 4.4, 95% CI, 2.9-5.0; p = 0.03). There were no differences in the proportions of patients experiencing end-organ injury (7%, n = seven of 102 versus 6%, n = four of 72; p = 0.72). With the numbers available, there was no difference in 90-day mortality rate between groups (1.9%, n = two of 102 versus 1.3%, n = one of 72; p = 0.77). We found that hypotensive epidural anesthesia resulted in less blood loss, fewer transfusions, and no apparent increase in serious complications in pelvic and sacral tumor surgery performed in the setting of a high-volume tertiary sarcoma referral hospital. We recommend that further collaborative studies be undertaken to confirm our results with hypotensive epidural anesthesia in surgery for pelvic tumors. Level III, therapeutic study.

Increased cardiac output, not pulmonary artery systolic pressure, increases intrapulmonary shunt in healthy humans breathing room air and 40% O2.

Blood flow through intrapulmonary arteriovenous anastomoses (IPAVAs) has been demonstrated to increase in healthy humans during a variety of conditions; however, whether or not this blood flow represents a source of venous admixture (Q̇ VA /Q̇T) that impairs pulmonary gas exchange efficiency (i.e. increases the alveolar-to-arterial PO2 difference (A-aDO2)) remains controversial and unknown. We hypothesized that blood flow through IPAVAs does provide a source of Q̇ VA /Q̇T. To test this, blood flow through IPAVAs was increased in healthy humans at rest breathing room air and 40% O2: (1) during intravenous adrenaline (epinephrine) infusion at 320ngkg(-1)min(-1) (320ADR), and (2) with vagal blockade (2mg atropine), before and during intravenous adrenaline infusion at 80ngkg(-1)min(-1) (ATR+80ADR). When breathing room air the A-aDO2 increased by 6±2mmHg during 320ADR and by 5±2mmHg during ATR+80ADR, and the change in calculated Q̇ VA /Q̇T was +2% in both conditions. When breathing 40% O2, which minimizes contributions from diffusion limitation and alveolar ventilation-to-perfusion inequality, the A-aDO2 increased by 12±7mmHg during 320ADR, and by 9±6mmHg during ATR+80ADR, and the change in calculated Q̇ VA /Q̇T was +2% in both conditions. During 320ADR cardiac output (Q̇T) and pulmonary artery systolic pressure (PASP) were significantly increased; however, during ATR+80ADR only Q̇T was significantly increased, yet blood flow through IPAVAs as detected with saline contrast echocardiography was not different between conditions. Accordingly, we suggest that blood flow through IPAVAs provides a source of intrapulmonary shunt, and is mediated primarily by increases in Q̇T rather than PASP.

Efficacy of Intramuscular Epinephrine for the Treatment of Severe Anaphylaxis: A Comparison of Two Ambulance Services with Different Protocols

Anaphylaxis is a severe multisystem hypersensitivity reaction. Although treatment with epinephrine is advocated, the evidence for this is limited. Ambulance services in Australasia vary in their approach to epinephrine use - conservative vs. aggressive treatment. We wished to observe and compare a conservative and an aggressive service. We examined demographics, clinical features, epinephrine use and outcomes in patients with anaphylaxis treated by two Australasian ambulance services over a 12-month period. These services differed substantially in their approaches to giving epinephrine. Service A treated 195 reactions and Service B treated 231. There account for 0.2% of acute ambulance responses in both services. There were similar distributions of age, sex, reaction triggers, ambulance response times and case times. Epinephrine was given prior to ambulance arrival in 55 (28%) and 33 (14%) in Services A and B respectively (p=0.0049). Reactions were severe on ambulance arrival in 51 (25%) in Service A compared to 58 (25%) in Service B. The rates of epinephrine administration were 38/144 (26%) and 39/51 (76%) for moderate and severe anaphylaxis respectively in Service A, compared to 16/173 (9.2%) and 11/58 (19%) in Service B (p<0.0001). Second doses of epinephrine were given to 13 (6.7%) in Service A, including 11 intravenous infusions of epinephrine. Service B gave no second doses of epinephrine. Major clinical features of anaphylaxis were unresolved by arrival in the emergency department (ED) in 29 (15%) compared to 28 (12%) in Services A and B respectively (p=0.455). We were unable to demonstrate any therapeutic benefit associated with higher rates of epinephrine usage where the primary route of administration was intramuscular. Randomized controlled trials comparing intramuscular injection with intravenous infusion and/or placebo are required.

Influence of detomidine and xylazine on spleen dimensions and on splenic response to epinephrine infusion in healthy adult horses

ObjectiveTo compare the changes in splenic length and thickness and in packed cell volume (PCV) following detomidine or xylazine administration and subsequent epinephrine infusion. Hypothesis: Spleen relaxation occurs following xylazine or detomidine administration and interferes with subsequent splenic contractile response to epinephrine. Study designRandomized non‐blinded crossover experimental study. Animals6 healthy adult mares. MethodsThe mares received an intravenous (IV) epinephrine infusion (1 μg kg−1minute−1 over 5 minutes) one hour after IV administration of detomidine (0.01 mg kg−1), xylazine (0.5 mg kg−1) or no drug (control), with a withdrawal period of at least 7 days between experiments. The splenic length measured in two different axes, the splenic thickness, and the PCV were measured prior to sedation (T0), 30 minutes later, and at 5‐minute intervals from the start of the epinephrine infusion (T1) until T1 + 40 minutes. Changes from base‐line and between treatments were compared using a two‐way anova for repeated measures. Significance was set at p < 0.05. ResultsSplenic length was significantly increased and PCV was significantly decreased after detomidine administration compared to baseline. Epinephrine infusion resulted in a significant decrease in splenic length and thickness, and a significant increase in PCV, irrespective of prior treatment with detomidine or xylazine. ConclusionsDetomidine administration was followed by a sonographically detectable increase of splenic length. Neither detomidine nor xylazine interfered with the ability of the spleen to contract following subsequent administration of an epinephrine infusion given one hour later. Clinical relevancePrevious sedation with alpha‐2 agonists does not preclude the efficiency of epinephrine as a medical treatment of left dorsal displacement of the large colon, but further investigations are required with other drug doses and different time intervals between administrations.

Direct demonstration that blood flow through intrapulmonary arteriovenous anastomoses worsens pulmonary gas exchange efficiency

Pulmonary gas exchange efficiency is defined and quantified by the alveolar‐arterial PO2 difference (AaDO2). Sources of venous admixture (QVA/QT) that increase AaDO2 are ventilation‐perfusion (V/Q) inequality, diffusion limitation, and shunt (QS/QT). Intravenous infusion of epinephrine (EPI) increases blood flow through intrapulmonary arteriovenous anastomoses (QIPAVA) in healthy humans at rest, as detected by saline contrast echocardiography, but whether or not this is a source of shunt remains controversial. We hypothesized that QIPAVA is a source of shunt, and therefore, AaDO2 would increase during EPI infusion in healthy humans at rest when QIPAVA is increased. From baseline to max EPI infusion (320 ng/kg/min), AaDO2 increased from 4.9 to 9.4 mmHg and QVA/QT increased from 2.8 to 3.8% in healthy subjects breathing room air (n=3). We repeated these measurements in the same subjects breathing 40% O2 which increases alveolar PO2 and reduces O2 equilibration time from ~0.6 to &lt;0.2 sec, thereby eliminating QVA/QT contributions from diffusion limitation and V/Q inequality, but still allowing for QIPAVA to occur. From baseline to max EPI infusion breathing 40% O2, AaDO2 increased from 17.3 to 23.7 mmHg and QS/QT increased from 4.4 to 5.4%. We conclude that QIPAVA is a source of shunt, because QVA/QT and QS/QT both increased by 1% during max EPI infusion. Support: American Heart Association Predoctoral Fellowship

Vascular and metabolic effects of adrenaline in adipose tissue in type 2 diabetes

Objective:The aim was to investigate adipose tissue vascular and metabolic effects of an adrenaline infusion in vivo in subjects with and without type 2 diabetes mellitus (T2DM).Design:Clinical intervention study with 1-h intravenous adrenaline infusion.Subjects:Eight male overweight T2DM subjects and eight male weight-matched, non-T2DM subjects were studied before, during and after an 1-h intravenous adrenaline infusion. Adipose tissue blood flow (ATBF) was determined by 133Xenon wash-out technique, and microvascular volume in the adipose tissue was studied by contrast-enhanced ultrasound imaging. Adipose tissue fluxes of glycerol, non-esterified fatty acids (NEFA), triacylglycerol and glucose were measured by Fick's principle after catherisation of a radial artery and a vein draining the abdominal, subcutaneous adipose tissue.Results:ATBF increased similarly in both groups during the adrenaline infusion. One hour post adrenaline, ATBF was still increased in overweight T2DM subjects. Adrenaline increased microvascular volume in non-T2DM subjects while this response was impaired in overweight T2DM subjects. Adrenaline-induced increase in lipolysis was similar in both groups, but NEFA output from adipose tissue was delayed in overweight T2DM subjects. Glucose uptake in adipose tissue increased in non-T2DM subjects during adrenaline infusion but was unchanged in overweight T2DM subjects. This results in a delayed excess release of NEFA from the adipose tissue in overweight T2DM subjects after cessation of the adrenaline infusion.Conclusion:Capillaries in the adipose tissue are recruited by adrenaline in non-T2DM subjects; however, this response is impaired in overweight T2DM subjects. NEFA, released in adipose tissue during adrenaline stimulation, is insufficiently re-esterified in situ in overweight T2DM subjects, probably owing to increased ATBF after adrenaline infusion and inability to increase adipose tissue glucose uptake.

The effects of low‐dose epinephrine infusion on spleen size, central and hepatic circulation and circulating platelets

In several conditions associated with adrenergic stimulation, an increase in peripheral count of larger platelets has been observed, but the mechanism remained elusive. Larger platelets have greater prothrombotic potential and increase the risk of acute thrombotic events. The human spleen retains one-third of total body platelets, with mean volume (MPV) about 20% greater than that of circulating platelets. We aimed to answer whether low-dose epinephrine infusion results in spleen contraction and MPV increase. We undertook the continuous ultrasonic measurements of spleen volume, hepatic and central circulation with concurrent blood sampling in response to intravenous infusion of epinephrine (6 min of 0·06 µg kg(-1) per min, followed by 3 min of 0·12 µg kg(-1) per min) in nine healthy young subjects. The spleen volume started to decrease immediately after the onset of infusion, in the presence of substantial decreases in peripheral resistance and mean blood pressure and increases in heart rate and cardiac output. The majority of spleen emptying, approximately 25%, (95% CI 71·3-299·7) was observed 1 min after infusion onset, the hepatic vein flow peaked at the end of infusion for 28·4% (95% CI 1074·6-407·9), while increases in platelet count for approximately 31% (95% CI 187·8-314·8) and MPV for 4·4% (95% CI 7·3-10·9) lagged until 1 min after infusion cessation. We suggest that spleen is a dynamic reservoir of large platelets, which are mobilized even by low-dose epinephrine infusion in conditions of decreased blood pressure.