Epinephrine, inodilator, or no inotrope in venoarterial extracorporeal membrane oxygenation implantation: a single-center experience.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) can be a rescue therapy for patients in cardiogenic shock or in refractory cardiac arrest. After cannulation, vasoplegia and cardiac depression are frequent. In literature, there are conflicting data on inotropic therapy in these patients. METHODS: Analysis of a retrospective registry of all patients treated with VA-ECMO in a university hospital center between October 2010 and December 2018 for cardiogenic shock or extracorporeal cardiopulmonary resuscitation (eCPR) with a focus on individual early inotropic therapy. RESULTS: A total of 231 patients (age 58.6 ± 14.3, 29.9% female, 58% eCPR, in-house survival 43.7%) were analyzed. Of these, 41.6% received no inotrope therapy within the first 24 h (survival 47.9%), 29.0% received an inodilator (survival 52.2%), and 29.0% received epinephrine (survival 25.0%). Survival of patients with epinephrine was significantly worse compared to other patient groups when evaluating 30-day survival (p = 0.034/p = 0.005) and cumulative incidence of in-hospital death (p = 0.001). In a multivariate logistic regression analysis, treatment with epinephrine was associated with mortality in the whole cohort (OR 0.38, p = 0.011) as well as after propensity score matching (OR 0.24, p = 0.037). We found no significant differences between patients with inodilator treatment and those without. CONCLUSION: Early epinephrine therapy within the first 24 h after cannulation for VA-ECMO was associated with poor survival compared to patients with or without any inodilator therapy. Until randomized data are available, epinephrine should be avoided in patients on VA-ECMO.

Expired Epinephrine Maintains Chemical Concentration and Sterility.

OBJECTIVES: Epinephrine shortages affect nearly all American emergency medical services (EMS) systems. Utilization of expired epinephrine could mitigate this situation in daily EMS operations. Concerns about using expired medications include sterility, potency, and potential harmful chemical decay byproducts. There are no cross-platform analyses of sterility and chemical purity of multiple samples of expired parenteral epinephrine. We hypothesized that epinephrine injections will remain sterile and will retain their active ingredient's content for more than 30 months past expiration. METHODS: Six parenteral epinephrine prefilled syringes, 1 mg/10 mL, with an expiration date of January 1, 2012 had been stored in the climate controlled setting of a hospital inpatient pharmacy where they remained until they were taken for chemical or microbial analysis 30 months after expiration. An unexpired parenteral epinephrine prefilled syringe content was used as a control. Contents of three separate syringes with expired content from the same lot and one control underwent ultra-high pressure liquid chromatography-mass spectrometry (UHPLC-MS) and nuclear magnetic resonance (NMR) to determine epinephrine content and stability. In parallel, contents of another three expired epinephrine syringes were analyzed for sterility by plating on aerobic, anaerobic, and fungal media in a hospital microbiology laboratory. The aerobic plates were checked for growth in 3 days, the anaerobic in 5 days, and the fungal in 28 days. RESULTS: UHPLC-MS and NMR showed that content of epinephrine present in the original sample remained unchanged compared to the control. There was no statistical difference in the UHPLC-MS and NMR signal amplitudes between the control and the expired samples. No chemical degradation byproducts were detected using NMR. There was no growth of any bacteria or fungus. CONCLUSION: Recurrent epinephrine shortages impact EMS and hospital operations in the United States. Individual administrators may be hesitant to authorize use of expired pharmaceuticals due to perceived potential complications or fear of litigation. This study shows that the original parenteral epinephrine remains sterile and detectably pure more than 2.5 years after expiration. Further study of the sterility and chemical integrity of expired medications that had been subjected to the conditions of EMS vehicles may be a future research endeavor based on the aforementioned paradigm.

The Impact of Freeze-Thaw Cycles on Epinephrine.

OBJECTIVES: Epinephrine is the first-line medical treatment for anaphylaxis, a life-threatening allergic syndrome. To treat anaphylaxis, backcountry recreationalists and guides commonly carry epinephrine autoinjectors. Epinephrine may be exposed to cold temperatures and freezing during expeditions. An epinephrine solution must contain 90% to 115% of the labeled epinephrine amount to meet United States Pharmacopeia standards. The purpose of this study was to determine whether freeze-thaw cycles alter epinephrine concentrations in autoinjectors labeled to contain 1.0 mg/mL epinephrine. A further objective was to determine whether samples continued to meet United States Pharmacopeia concentration standards after freeze-thaw cycles. METHODS: Epinephrine from 6 autoinjectors was extracted and divided into experimental and control samples. The experimental samples underwent 7 consecutive 12-hour freeze cycles followed by 7 12-hour thaw cycles. The control samples remained at an average temperature of 23.1°C for the duration of the study. After the seventh thaw cycle, epinephrine concentrations were measured using a high-performance liquid chromatography assay with mass spectrometry detection. RESULTS: The mean epinephrine concentration of the freeze-thaw samples demonstrated a statistically significant increase compared with the control samples: 1.07 mg/mL (SD ± 8.78; 95% CI, 1.04 to 1.11) versus 0.96 mg/mL (SD ± 6.81; 95% CI, 0.94 to 0.99), respectively. The maximal mean epinephrine concentration in the experimental freeze-thaw group was 1.12 mg/mL, which still fell within the range of United States Pharmacopeia standards for injectables (0.90 to 1.15 mg/mL). CONCLUSIONS: Although every attempt should be made to prevent freezing of autoinjectors, this preliminary study demonstrates that epinephrine concentrations remain within 90% to 115% of 1.0 mg/mL after multiple freeze-thaw cycles.

Pharmacotherapy in refractory anaphylaxis: when intramuscular epinephrine fails.

PURPOSE OF REVIEW: This review aims to provide an evidence-based overview of several pharmacotherapeutic options available for refractory anaphylaxis when intramuscular epinephrine, the drug of choice, fails to provide resolution of signs and symptoms. RECENT FINDINGS: The evidence base for the therapy of anaphylaxis is comparatively weak and is largely based on consensus expert recommendations and case reports. There is an increasing recognition that this is problematic. The level of evidence for epinephrine use in anaphylaxis is higher than for other agents. Recent systematic reviews have confirmed the lack of high-grade evidence to support use of antihistamines and corticosteroids in anaphylaxis, both of which statistically continue to be used more frequently than epinephrine. Newer pharmacotherapeutic agents have been proffered, but none has been evaluated with scientific rigor. SUMMARY: Some anaphylactic reactions are so severe that treatment is unsuccessful despite rapid recognition and treatment. Improving the evidence base for the various treatment modalities may further help minimize fatalities once anaphylaxis is recognized. Consensus expert recommendations and case reports suggest a number of pharmacotherapeutic agents that are worthy of high-quality scrutiny through randomized controlled studies in which both treatment and placebo arms receive intramuscular epinephrine injections.

Medication errors in prehospital management of simulated pediatric anaphylaxis.

BACKGROUND: Systematic evaluation of the performances of prehospital providers during actual pediatric anaphylaxis cases has never been reported. Epinephrine medication errors in pediatric resuscitation are common, but the root causes of these errors are not fully understood. OBJECTIVE: The primary objective of this study was to identify underlying causes of prehospital medication errors that were observed during a simulated pediatric anaphylaxis reaction. METHODS: Two- and 4-person emergency medical services crews from eight geographically diverse agencies participated in a 20-minute simulation of a 5-year old child with progressive respiratory distress and hypotension from an anaphylactic reaction. Crews used their own equipment and drugs. A checklist-based scoring protocol was developed to help identify errors. A trained facilitator conducted a structured debriefing, supplemented by playback of video recordings, immediately after the simulated event to elicit underlying causes of errors. Errors were analyzed with mixed quantitative and qualitative methods. RESULTS: One hundred forty-two subjects participated in 62 simulation sessions. Ninety-five percent of crews (59/62) gave epinephrine, but 27 of those crews (46%) delivered the correct dose of epinephrine in an appropriate concentration and route. Twelve crews (20%) gave a dose that was ≥5 times the correct dose; 8 crews (14%) bolused epinephrine intravenously. Among the 55 crews who gave diphenhydramine, 4 delivered the protocol-based dose. Three crews provided an intravenous steroid, and 1 used the protocol-based dose. Underlying causes of errors were categorized into eight themes: faulty reasoning, weight estimation errors, faulty recall of medication dosages, problematic references, calculation errors, dose estimation, communication errors, and medication delivery errors. CONCLUSION: Simulation, followed by a structured debriefing, identified multiple, underlying causes of medication errors in the prehospital management of pediatric anaphylactic reactions. Sequential and synergistic errors were observed with epinephrine delivery.

Impact of temperature exposure on stability of drugs in a real-world out-of-hospital setting.

STUDY OBJECTIVE: The aim of this study is to determine the content of 5 important emergency medical services (EMS) drugs after being stored at the recommended refrigerated temperature, room temperature, or in an emergency physician transport vehicle operating under real-world working conditions. METHODS: Adrenaline hydrochloride, cisatracurium besylate, lorazepam, methylergonovine maleate, and succinylcholine chloride were stored for 1 year under the 3 conditions. For each storage condition, samples of the drugs were taken after 1, 2, 3, and 4 weeks and after 2, 4, 6, 8, 10, and 12 months. For adrenaline hydrochloride, however, the samples were taken after 1, 2, 4, 6, 8, 10, and 12 months. The samples were analyzed with a validated high-performance liquid chromatography assay. A drug was considered stable if its content was above 90%. RESULTS: Adrenaline hydrochloride and methylergonovine maleate remained stable for 1 year at room temperature and in the emergency physician transport vehicle. At room temperature and in the emergency physician transport vehicle, lorazepam became unstable within 4 weeks. Succinylcholine chloride was stable for 2 months at room temperature and for 1 month in the emergency physician transport vehicle. Cisatracurium besylate became unstable within 4 months at room temperature. However, it remained stable for 4 months in the emergency physician transport vehicle. CONCLUSION: When stored at room temperature or in the emergency physician transport vehicle, lorazepam became unstable within weeks, whereas succinylcholine chloride and cisatracurium besylate became unstable within months. Adrenaline hydrochloride and methylergonovine maleate remained stable for several months, even under room temperature and emergency physician transport vehicle conditions. Thus, real-world EMS working conditions pose challenges for maintaining optimal efficacy of these important EMS drugs.

Managing the student with severe food allergies.

School nurses play a key role in managing students with food allergies. It is becoming more common to encounter students with severe allergies to multiple foods, putting them at risk for anaphylaxis. It is essential that the school nurse have a clear understanding of food allergies and how to effectively manage students in the school setting. Effective communication between families, health care providers, faculty, staff, and students, is of utmost importance when developing a plan of care to ensure the safety of the student with food allergies. Using an interdisciplinary approach to case management, the school nurse can develop comprehensive individualized health care plans for all students with food allergies.

The use of epinephrine for out-of-hospital treatment of anaphylaxis: resource document for the National Association of EMS Physicians position statement.

Anaphylaxis is a potentially life-threatening condition that requires both prompt recognition and treatment with epinephrine. All levels of emergency medical services (EMS) providers, with appropriate physician oversight, should be able to carry and properly administer epinephrine safely when caring for patients with anaphylaxis. EMS systems and EMS medical directors should develop a mechanism to review the charts of patients who received epinephrine and were not in cardiac arrest. This will help to ensure the safe and appropriate use of epinephrine in order to provide continued quality improvement. Despite the safety of epinephrine, EMS systems that carry epinephrine autoinjectors should establish protocols to deal with patients or emergency responders who have an unintentional injection of epinephrine into the hand or digit. Continued research is needed to better define the role that EMS plays in the management of anaphylaxis. This paper serves as a resource document to the National Association of EMS Physician position on the use of epinephrine for the out-of-hospital treatment of anaphylaxis. Key words: EMS; prehospital; anaphylaxis; epinephrine; intramuscular epinephrine.

The use of epinephrine for out-of-hospital treatment of anaphylaxis.

The National Association of EMS Physicians (NAEMSP) believes that all levels of emergency medical services (EMS) providers should be allowed to carry and administer epinephrine for the treatment of anaphylaxis. This document is the official position of the NAEMSP.

[Epinephrine Bitartrate Reference Standard (Control 951) of National Institute of Health Sciences].

The raw material for epinephrine bitartrate was tested for preparation of the "Epinephrine Bitartrate Reference Standard (Control 951)" of National Institute of Health Sciences. Analytical data obtained were as follows: melting point, 148.6 degrees C (decomposition); UV spectrum, lambda max = 279 nm; IR spectrum, the same as that of JP Epinephrine Bitartrate Reference Standard (Control 792); optical rotation, [alpha]20D = -52.8 degrees; thin-layer chromatography, one impurity was detected; high-performance liquid chromatography, no impurity was detected; loss on drying, 0.01%; assay, 99.6% by potentiometric titration, 100.3% by spectrophotometry. Based on the above results, the raw material was authorized as the Epinephrine Bitartrate Reference Standard (Control 951) of National Institute of Health Sciences (Japanese Pharmacopoeia).

Labor pain relief using bupivacaine and sufentanil: patient controlled epidural analgesia versus intermittent injections.

OBJECTIVES: To determine whether the use of patient-controlled epidural analgesia (PCEA) versus intermittent injections (CIT) resulted in local anesthetic dose reduction. STUDY DESIGN: PCEA and CIT using a mixture of 0.125% bupivacaine with sufentanil 1 or 0.75 microgram/ml were compared in 60 and 195 parturients, respectively. Assessments included pain scores, local anesthetic consumption, degree of motor blockade, type of delivery and neonatal outcome. Statistical analysis was done using Student's t test and Chi-squares. RESULTS: PCEA and CIT provided effective analgesia during labor and delivery. A higher dose of opioid significantly reduced the use of local anesthetic solution in PCEA-patients. There was no difference in motor blockade, type of delivery and neonatal outcome. CONCLUSION: Patient-controlled epidural analgesia is an effective, safe and acceptable alternative to conventional intermittent epidural injections for pain relief during labor and delivery.