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Medline ® Abstracts for References 10,17-21,28,29

of 'Anaphylaxis: Emergency treatment'

10
TI
Epinephrine and its use in anaphylaxis: current issues.
AU
Simons KJ, Simons FE
SO
Curr Opin Allergy Clin Immunol. 2010;10(4):354.
 
PURPOSE OF REVIEW: Epinephrine is a life-saving medication in the treatment of anaphylaxis, in which it has multiple beneficial pharmacologic effects. Here, we examine the evidence base for its primary role in the treatment of anaphylaxis episodes in community settings.
RECENT FINDINGS: We review the practical pharmacology of epinephrine in anaphylaxis, its intrinsic limitations, and the pros and cons of different routes of administration. We provide a new perspective on the adverse effects of epinephrine, including its cardiac effects. We describe the evidence base for the use of epinephrine in anaphylaxis. We discuss the role of epinephrine auto-injectors for treatment of anaphylaxis in community settings, including identification of patients who need an auto-injector prescription, current use of auto-injectors, and advances in auto-injector design. We list reasons why physicians fail to prescribe epinephrine auto-injectors for patients with anaphylaxis, and reasons why patients fail to self-inject epinephrine in anaphylaxis. We emphasize the primary role of epinephrine in the context of emergency preparedness for anaphylaxis in the community.
SUMMARY: Epinephrine is the medication of choice in the first-aid treatment of anaphylaxis in the community. For ethical reasons, it is not possible to conduct randomized, placebo-controlled trials of epinephrine in anaphylaxis; however, continued efforts are needed towards improving the evidence base for epinephrine injection in this potentially fatal disease.
AD
Faculty of Pharmacy and Department of Pediatrics&Child Health, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
PMID
17
TI
Insect sting anaphylaxis; prospective evaluation of treatment with intravenous adrenaline and volume resuscitation.
AU
Brown SG, Blackman KE, Stenlake V, Heddle RJ
SO
Emerg Med J. 2004;21(2):149.
 
OBJECTIVES: To assess a protocol for treatment of sting anaphylaxis.
DESIGN: Prospective assessment of treatment with oxygen, intravenous infusion of adrenaline (epinephrine), and volume resuscitation with normal saline.
SETTING: Sub-study of a venom immunotherapy trial.
PARTICIPANTS: 21 otherwise healthy adults with systemic allergic reactions to diagnostic sting challenge.
MAIN OUTCOME MEASURES: Response to treatment, total adrenaline dose and infusion duration, recurrence of symptoms after stopping the infusion, and additional volume resuscitation.
RESULTS: 19 participants required intervention according to the protocol. All received adrenaline, and five received volume resuscitation. In nine cases, physical signs of anaphylaxis recurred after initial attempts at stopping adrenaline but resolved after recommencing the infusion. The median total dose and infusion duration were 590 micro g and 115 minutes respectively, but were significantly higher for eight patients who had hypotensive reactions (762 micro g and 169 minutes respectively). Hypotension was always accompanied by a relative bradycardia, which was severe and treated with atropine in two patients. Widespread T wave inversion occurred, before starting treatment with adrenaline, in one person with an otherwise mild reaction. All patients fully recovered and were fit for same day discharge, apart from the person with ECG changes who was observed overnight and discharged the following day.
CONCLUSIONS: Carefully titrated intravenous adrenaline combined with volume resuscitation is an effective strategy for treating sting anaphylaxis, however severe bradycardia may benefit from additional treatment with atropine. Cardiac effects of anaphylaxis, perhaps including neurocardiogenic mechanisms, may be an important factor in some lethal reactions.
AD
Department of Emergency Medicine, Royal Hobart Hospital, Hobart, Australia. simon.brown@health.wa.gov.au<simon.brown@health.wa.gov.au>
PMID
18
TI
First-aid treatment of anaphylaxis to food: focus on epinephrine.
AU
Simons FE
SO
J Allergy Clin Immunol. 2004;113(5):837.
 
Avoiding food triggers for anaphylactic reactions (severe acute systemic allergic reactions) is easier said than done. Most episodes of anaphylaxis to food occur unexpectedly in the community in the absence of a health care professional. All individuals at risk should therefore have an emergency action plan in place. The cornerstone of first-aid treatment of anaphylaxis is epinephrine injected intramuscularly in the vastus lateralis muscle (lateral aspect of the thigh). In this review, we focus on epinephrine. We examine a therapeutic dilemma: the issue of epinephrine dose selection in an individual for whom no optimal fixed-dose auto-injector formulation exists, and a therapeutic controversy: the issue of epinephrine injection versus an oral H1-antihistamine in anaphylaxis episodes that appear to be mild. The pharmaceutical industry could address the first of these issues by providing a wider range of epinephrine fixed doses in easy-to-use auto-injectors, or by providing adjustable epinephrine doses in auto-injectors. The second issue could be addressed in part by development of alternative routes of epinephrine administration for the first-aid, out-of-hospital treatment of anaphylaxis.
AD
Section of Allergy and Clinical Immunology, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada R3A 1R9. lmcniven@hsc.mb.ca
PMID
19
TI
Epinephrine absorption in adults: intramuscular versus subcutaneous injection.
AU
Simons FE, Gu X, Simons KJ
SO
J Allergy Clin Immunol. 2001;108(5):871.
 
We report a prospective, randomized, blinded, placebo-controlled, 6-way crossover study of intramuscular versus subcutaneous injection of epinephrine in young men. Peak plasma epinephrine concentrations were significantly higher (P<.01) after epinephrine was injected intramuscularly into the thigh than after epinephrine was injected intramuscularly or subcutaneously into the upper arm. We recommend intramuscular injection of epinephrine into the thigh as the preferred route and site of injection of this life-saving medication in the initial treatment of anaphylaxis.
AD
Section of Allergy&Clinical Immunology, Department of Pediatrics&Child Health, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
PMID
20
TI
Epinephrine absorption in children with a history of anaphylaxis.
AU
Simons FE, Roberts JR, Gu X, Simons KJ
SO
J Allergy Clin Immunol. 1998;101(1 Pt 1):33.
 
BACKGROUND: Prompt injection of epinephrine is the cornerstone of systemic anaphylaxis treatment. The rate of epinephrine absorption has not been reported previously in allergic children.
OBJECTIVE: Our objective was to study the clinical pharmacology of epinephrine in this population.
METHODS: We performed a prospective, randomized, blinded, parallel-group study in 17 children with a history of anaphylaxis to food, Hymenoptera venom, or other substances. We injected 0.01 ml/kg epinephrine solution (maximum 0.3 ml [0.3 mg]) subcutaneously, or 0.3 mg epinephrine intramuscularly from an autoinjector. Plasma epinephrine concentrations, heart rate, blood pressure, and adverse effects were monitored.
RESULTS: In nine children who received epinephrine subcutaneously, the mean maximum plasma epinephrine concentration (+/- SEM) was 1802 +/- 214 pg/ml, achieved at a mean time of 34 +/- 14 minutes (range, 5 to 120 minutes). Only two of the nine children achieved maximum plasma concentrations by 5 minutes. In eight children who received epinephrine intramuscularly, the mean maximum plasma concentration was 2136 +/- 351 pg/ml, achieved at a mean time of 8 +/- 2 minutes, which was significantly faster than the mean time at which maximum plasma concentrations were achieved after subcutaneous epinephrine injection (p<0.05). Six of the eight children achieved maximum plasma concentrations by 5 minutes. The terminal elimination half-life was 43 +/- 15 minutes. No serious adverse effects were noted in any child.
CONCLUSIONS: In children, recommendations for subcutaneous epinephrine injection are based on anecdotal experience, and should be reevaluated in view of our finding of delayed epinephrine absorption when this route is used. This delay might have important clinical implications during an episode of systemic anaphylaxis. The intramuscular route of injection is preferable.
AD
Department of Pediatrics and Child Health, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
PMID
21
TI
Fatal posture in anaphylactic shock.
AU
Pumphrey RS
SO
J Allergy Clin Immunol. 2003;112(2):451.
 
AD
PMID
28
TI
The pathophysiology of shock in anaphylaxis.
AU
Brown SG
SO
Immunol Allergy Clin North Am. 2007;27(2):165.
 
The balance of evidence from human observations and animal studies suggests that the main pathophysiologic features of anaphylactic shock are a profound reduction in venous tone and fluid extravasation causing reduced venous return (mixed hypovolemic-distributive shock) and depressed myocardial function. Aggressive fluid resuscitation is required to ameliorate hypovolemic-distributive shock, and an intravenous infusion of epinephrine will increase vascular tone, myocardial contractility, and cardiac output in most cases. Where these measures fail, pathophysiologic considerations and anecdotal evidence support the consideration of selective vasoconstrictors as the next step in treatment.
AD
Emergency Medicine Research Unit, The University of Western Australia and Fremantle Hospital, Alma Street, Fremantle, WA 6160, Australia. simon.brown@uwa.edu.au
PMID
29
TI
Anaphylaxis: clinical concepts and research priorities.
AU
Brown SG
SO
Emerg Med Australas. 2006;18(2):155.
 
Anaphylaxis is a severe immediate-type hypersensitivity reaction characterized by life-threatening upper airway obstruction bronchospasm and hypotension. Although many episodes are easy to diagnose by the combination of characteristic skin features with other organ effects, this is not always the case and a workable clinical definition of anaphylaxis and useful biomarkers of the condition have been elusive. A recently proposed consensus definition is ready for prospective validation. The cornerstones of management are the supine position, adrenaline and volume resuscitation. An intramuscular dose of adrenaline is generally recommended to initiate treatment. If additional adrenaline is required, then a controlled intravenous infusion might be more efficacious and safer than intravenous bolus administration. Additional bronchodilator treatment with continuous salbutamol and corticosteroids are used for severe and/or refractory bronchospasm. Aggressive volume resuscitation, selective vasopressors, atropine (for bradycardia), inotropes that bypass the beta-adrenoreceptor and bedside echocardiographic assessment should be considered for hypotension that is refractory to treatment. Management guidelines continue to be opinion- and consensus-based, with retrospective studies accounting for the vast majority of clinical research papers on the topic. The clinical spectrum of anaphylaxis including major disease subgroups requires clarification, and validated scoring systems and outcome measures are needed to enable good-quality prospective observational studies and randomized controlled trials. A systematic approach with multicentre collaboration is required to improve our understanding and management of this disease.
AD
Discipline of Emergency Medicine, The University of Western Australia and Fremantle Hospital, Fremantle, Western Australia, Australia. simon.brown@uwa.edu.au
PMID