Practice Parameter
Anaphylaxis d a practice parameter update 2015
Phillip Lieberman,MD;Richard A.Nicklas,MD;Christopher Randolph,MD;John Oppenheimer,MD;
David Bernstein,MD;Jonathan Bernstein,MD;Anne Ellis,MD;David B.K.Golden,MD;Paul Greenberger,MD;Steven Kemp,MD;David Khan,MD;Dennis Ledford,MD;Jay Lieberman,MD;Dean Metcalfe,MD;
Anna Nowak-Wegrzyn,MD;Scott Sicherer,MD;Dana Wallace,MD;Joann Blessing-Moore,MD;David Lang,MD;Jay M.Portnoy,MD;Diane Schuller,MD;Sheldon Spector,MD;and Stephen A.Tilles,MD
Chief Editors:Phillip Lieberman,MD;Richard A.Nicklas,MD;John Oppenheimer,MD;Christopher Randolph,MD Members of the Joint Task Force:David Bernstein,MD;Joann Blessing-Moore,MD;David Khan,MD;
David Lang,MD;Richard Nicklas,MD;John Oppenheimer,MD;Jay M.Portnoy,MD;Christopher Randolph,MD;Diane Schuller,MD;Sheldon Spector,MD;Stephen A.Tilles,MD;Dana Wallace,MD
Practice Parameter Workgroup:David Bernstein,MD;Jonathan Bernstein,MD;Anne Ellis,MD;David B.K.Golden,MD;David Khan,MD;Dennis Ledford,MD;Jay Lieberman,MD;Dean Metcalfe,MD;Dana Wallace,MD
This parameter was developed by the Joint Task Force on Practice Parameters,representing the American Academy of Allergy,Asthma and Immunology;the American College of Allergy,Asthma and Immunology;and the Joint Council of Allergy,Asthma and Immunology.
Reprints:Susan L.Grupe,Joint Task Force on Practice Parameters,50N Brockway Street,#304,Palatine,IL 60067;E-mail:SueGrupe@https://www.doczj.com/doc/3c11467090.html, .
Disclaimer:The American Academy of Allergy,Asthma and Immunology (AAAAI)and the American College of Allergy,Asthma and Immunology (ACAAI)have jointly accepted responsibility for establishing “Anaphylaxis d A Practice Parameter Update 2015.”This is a complete and comprehensive document at the current time.The medical environment is a changing environment,and not all recommendations will be appropriate for all patients.Because this document incorporated the efforts of many par-ticipants,no single individual,including those who served on the Joint Task Force,is authorized to provide an of ?cial AAAAI or ACAAI interpretation of these practice parameters.Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Of ?ces of the AAAAI,the ACAAI,and the Joint Council of Allergy,Asthma and Immunology.These parameters are not designed for use by pharmaceutical companies in drug promotion.All practice parameters are available online at https://www.doczj.com/doc/3c11467090.html, or https://www.doczj.com/doc/3c11467090.html, .
Disclosures:The following is a summary of interests disclosed on work group members ’Con ?ict of Interest Disclosure Statements (not including information concerning family member interests).Completed Con ?ict of Interest Disclosure Statements are available upon request.David Bernstein,MD,is on the advisory boards of Teva and Circassion;is on the board of the American Board of Allergy and Immunology;is a consultant for Proctor &Gamble,Science Strategies,Guidepoint Federal,and Merck;provides legal support for Fowler,Whited,&Barrett;is speaker for Merck;and has received ?nancial support from the Centers for Disease Control and Prevention and the National Institute for Occu-pational Safety and Health (principal investigator)and Teva,Merck,Glaxo,P ?zer,Genentech,Novartis,Astra Zeneca,Amgon,Savoy,and Cephalon.Jonathan Bernstein,MD,has consulted for and received honorarium and gifts from Sano ?Aventis;served as consultant,speaker and researcher for Dyax,Shire,CSL Behring,ViroPharma,and research for Pharming,is the editor of the Journal of Asthma;serves on the AAAAI Board of Directors;is a committee member of the ACAAI,and is chair of the Allergists for Israel.Anne Ellis,MD,is s speaker for P ?zer Canada,Merck,and Astra;is on the advisory board of Palladin Labs;received a research grant from Circassia Ltd;and is on the Drug,Allergy &Anaphylaxis Committee of the ACAAI.David B.K.Golden,MD,is a consultant for Sano ?and GlaxoSmithKline,speaker for Genentech,and has received ?nancial support from Siemens for a clinical trial.Paul Greenberger,MD,has consulted for Mylan (Day)and is a committee member of the Food and Drug Administration Pulmonary Allergy Drugs Advisory Committee.Kevin J.Kelly,MD,received research grants from Targacept,Merck Schering,Schering,Chiltern,and Glaxo;has consulted for the University of North Carolina;and is a leadership board member of the American Lung Association of Wisconsin.Steven Kemp,MD,is a committee member,assembly member,and speaker for the AAAAI;is an editorial board member and committee member of the ACAAI;and is on the board of directors for the American Board of Allergy &Immunology.David Khan,MD,is a speaker for Baxter and Genentech.Dennis Ledford,MD,is a speaker for the South Carolina Allergy &Immunology Society and Meda Pharmaceutical;has received research grants from Teva,Forest,Genentech,Merck,and ViroPharma;has consulted for Shook Hardy Bacon,Saieva and Stine,and Genentech;is on the advisory board of AstraZeneca.Jay Lieberman,MD,reports no con ?icts.Philip Lieberman,MD,consults for Sano ?Aventis,Neyian,Merck,Genentech,Teva,Meda,and the Asthma and Allergy Foundation of America;serves on the advisory boards of Sano ?Aventis,Neyian,Merck,Teva,and Meda;and served as speaker for Neyina,Teva,and Meda.Dean Metcalfe,MD,reports no con ?icts.Anna Nowak-Wegrzyn,MD,is on the advisory boards of Merck and Nutricia;has served as speaker for Thermo ?sher Scienti ?c;and received a research grant from Nutucia.Scott Sicherer,MD,consults for Novartis;edits and receives honorarium from the Journal of Allergy and Clinical Immunology and is associate editor of the Journal of Allergy and Clinical Immunology In Practice;serves as speaker for and receives honorarium from the American Academy of Pediatrics;received honorarium from the American Board of Allergy and Immunology;is on the advisory board of Sano ?;edits and contributes to UpToDate;consults for the Food Allergy Initiative;received research grants from the National Institute of Allergy and Infectious Diseases,National Institutes of Health;is on the executive committee of the American Academy of Pediatrics;and is a medical advisor for the Food Allergy and Anaphylaxis Network and Food Allergy Research and Education.Dana Wallace,MD,is on the advisory board of Sano ?,Sunovion,and Mylan;serves as speaker for Sunovion,Teva,and Meda;and is on the board of directors of the World Allergy Organization.The Joint Task Force recognizes that experts in a ?eld are likely to have interests that could come into con ?ict with development a completely unbiased and objective practice parameter.To take advantage of that expertise,a process has been developed to prevent potential con ?icts from in ?uencing the ?nal document in a negative way.At the workgroup level,members who have a potential con ?ict of interest do not participate in discussions concerning topics related to the potential con ?ict;or if they do write a section on that topic,the workgroup completely rewrites it without their involvement to remove potential bias.In addition,the entire document is reviewed by the Joint Task Force and any apparent bias is removed at that level.Moreover,the
practice Contents lists available at
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https://www.doczj.com/doc/3c11467090.html,/10.1016/j.anai.2015.07.019
Ann Allergy Asthma Immunol 115(2015)341e 384
Classi ?cation of Recommendations and Evidence
Recommendation Rating Scale
Category of Evidence
Ia Evidence from meta-analysis of randomized controlled trials Ib Evidence from at least 1well-designed randomized controlled trial
Ic Evidence from at least 1randomized controlled trial that was not very well designed
IIa Evidence from at least 1controlled study without
randomization
IIb Evidence from at least 1other type of quasi-experimental
study
IIc Evidence from one of the above that was not very well
designed
IIIa Evidence from well-designed nonexperimental descriptive
studies,such as comparative studies
IIIb Evidence from nonexperimental descriptive studies,such as
comparative studies,that were not very well designed
Frequently,there can be a separation between the strength of recommendation and quality of evidence.parameter is sent for review by invited reviewers and by anyone with an interest in the topic by posting the document on the Web sites of the ACAAI and the AAAAI.
The Joint Task Force has made a concerted effort to acknowledge all contributors to this parameter.If any contributors have been excluded inadvertently,the Task Force will ensure that appropriate recognition of such contributions is made subsequently.
Chief Editor:Phillip Lieberman,MD,Clinical Professor of Medicine and Pediatrics,University of Tennessee College of Medicine,Memphis,Tennessee.Joint Task Force Liaison:Richard A.Nicklas,MD,Clinical Professor of Medicine,George Washington Medical Center,Washington,DC.Joint Task Force Members:David I.Bernstein,MD,Professor of Clinical Medicine and Environmental Health,Division of Allergy/Immunology,University of Cincinnati College of Medicine,Cincinnati,Ohio;Joann Blessing-Moore,MD,Adjunct Professor of Medicine and Pediatrics,Stanford University Medical Center,Department of Immunology,Palo Alto,California;David A.Khan,MD,Associate Professor of Internal Medicine,University of Texas Southwestern Medical Center,Dallas,Texas;David https://www.doczj.com/doc/3c11467090.html,ng,MD,Head,Allergy/Immunology Section,Division of Medicine,Director,Allergy and Immunology Fellowship Training Program,Cleveland Clinic Foundation,Cleveland,Ohio;Richard A.Nicklas,MD,Clinical Professor of Medicine,George Washington Medical Center,Washington,DC;John Oppenheimer,MD,Department of Internal Medicine,New Jersey Medical School,Pulmonary and Allergy Associates,Morristown,New Jersey;Jay M.Portnoy,MD,Director,Division of Allergy,Asthma &Immunology,The Children ’s Mercy Hospital,Professor of Pediatrics,University of Missouri e Kansas City School of Medicine,Kansas City,Missouri;Christopher C.Randolph,MD,Clinical Professor of Pediatrics,Yale Af ?liated Hospitals,Center for Allergy,Asthma,&Immunology,Waterbury,Connecticut;Diane E.Schuller,MD,Emeritus,Professor of Pediatrics,Emeritus Chief of Allergy and Immunology,Pennsylvania State University Milton S.Hershey Medical College,Hershey,Pennsylvania;Sheldon L.Spector,MD,Clinical Professor of Medicine,UCLA School of Medicine,Los Angeles,California;Stephen A.Tilles,MD,Clinical Assistant Professor of Medicine,University of Washington School of Medicine,Redmond,Washington;Dana Wallace,MD,Assistant Clinical Professor of Medicine,Nova Southeastern University College of Osteopathic Medicine,Davie,Florida.Parameter Workgroup Members:David Bernstein,MD,Professor of Clinical Medicine and Environmental Health,Division of Allergy/Immunology,University of Cincinnati College of Medicine,Cincinnati,Ohio;Jonathan Bernstein,MD,Professor of Clinical Medicine,University of Cincinnati College of Medicine,Department of Internal Medicine,Division of Immunology/Allergy Section,Director of Clinical Research,Editor-in-Chief Journal of Asthma,Cincinnati,Ohio;Anne Ellis,MD,MSc,FRCPC,Associate Professor and Chair,Division of Allergy &Immunology,Department of Medicine,Department of Biomedical &Molecular Sciences,Queen ’s University,Kingston,Ontario,Canada;David B.K.Golden,MD,Associate Professor of Medicine,Johns Hopkins University,Baltimore,Maryland;Paul A.Greenberger,MD,Professor of Medicine,Division of Allergy-Immunology,Northwestern University Feinberg School of Medicine,Chicago,Illinois;Steven Kemp,MD,Professor of Medicine,College of Medicine,University of Mississippi,Jackson,Mississippi;David Khan,MD,Associate Professor of Internal Medicine,University of Texas Southwestern Medical Center,Dallas,Texas;Dennis Ledford,MD,FAAAAI,FACAAI,Ellsworth and Mabel Simmons Professor of Allergy/Immunology,Morsani College of Medicine,University of South Florida,and James A.Haley VA Hospital,Tampa,Florida;Jay Lieberman,MD,Assistant Professor of Pediatrics,College of Medicine,University of Tennessee,Memphis,Tennessee;Dean Metcalfe,MD,Chief,Laboratory of Allergic Disease,Chief,Mast Cell Biology Section/LAD,National Institute of Allergy and Infectious Diseases,National Institutes of Health,Bethesda,Maryland;Anna Nowak-Wegrzyn,MD,Associate Professor of Pediatrics,Icahn School of Medicine at Mount Sinai,Division of Pediatric Allergy and Immunology,Jaffe Food Allergy Institute,New York,New York;Scott Sicherer,MD,Department of Pediatrics,Pediatric Allergy and Immunology,Icahn School of Medicine at Mount Sinai,Jaffee Food Allergy Institute,New York,New York;Dana Wallace,MD,Assistant Clinical Professor of Medicine,Nova Southeastern University College of Osteopathic Medicine,Davie,
Florida.
P.Lieberman et al./Ann Allergy Asthma Immunol 115(2015)341e 384
342
IVa Evidence from expert committee reports and/or opinions or clinical experience of respected authorities
Strength of Evidence*
A Directly based on category I evidence that is well designed
B Directly based on category II evidence or recommendation
from category I evidence that is not well designed
C Directly based on category III evidence or recommendation
from category II evidence that is not well designed
D Directly based on category IV or recommendation from cate-
gory III evidence that is not well designed
LB Laboratory based
NR Not rated
How This Practice Parameter was Developed
The Joint Task Force on Practice Parameters
The Joint Task Force on Practice Parameters(JTF)is a13-member task force consisting of6representatives assigned by the American Academy of Allergy,Asthma&Immunology;6by the American College of Allergy,Asthma&Immunology;and1by the Joint Council of Allergy and Immunology.This JTF oversees the development of practice parameters;selects the workgroup chair(s);and reviews drafts of the parameters for accuracy,prac-ticality,clarity,and broad utility of the recommendations for clinical practice.
The Anaphylaxis Parameter Workgroup
The Anaphylaxis Practice Parameter Workgroup was commissioned by the JTF to update the previous practice parameter.Dr Philip Lieberman invited workgroup members to participate in the parameter update who are considered experts in the?eld of anaphylaxis.Workgroup members have been vetted for?nancial con?icts of interest by the JTF and their con?icts of interest have been listed in this document and are posted on the JTF Web site(https://www.doczj.com/doc/3c11467090.html,). Where a potential con?ict of interest is present,the potentially con?icted workgroup member was excluded from discussing relevant issues.
Protocol for Finding Evidence
The charge to the workgroup was to use a systematic literature review,in conjunction with consensus expert opinion and workgroup-identi?ed supplementary documents,to update the Practice Parameter on Anaphylaxis.
A search of the medical literature since2010(the date of the last edition of this parameter)was performed for different terms that were considered relevant to this practice parameter.In particular,search terms included anaphylaxis,seminal?uid anaphylaxis,perioperative anaphylaxis,food allergy,mastocytosis, mast cell activation syndrome,idiopathic anaphylaxis,galactose1-3 alpha galactose,epinephrine,hymenoptera allergy,latex allergy, anaphylactic shock,exercise anaphylaxis,drug allergy,and immunotherapy.
An electronic search of databases,mainly PubMed,but also CENTRAL(Cochrane Central Register of Controlled Trials),Google Scholar,and Science Direct,was performed.In total3,424refer-ences were found.These were rated by giving preference for se-lection in the following order:meta-analysis,systematic reviews, randomized controlled trials,cohort studies,case e control studies, case series and case reports,and animal https://www.doczj.com/doc/3c11467090.html,ing these Abbreviations
Preface
This is the fourth iteration of this parameter entitled“The Diagnosis and Management of Anaphylaxis.”The?rst anaphylaxis parameter was published in1998and the last in2010.The objective of this parameter is to update these previous versions and ulti-mately to improve the care of patients by providing the practicing physician with an evidence-based approach to the diagnosis and management of anaphylactic events.
As always,the JTF and the contributing authors thank the ACAAI, AAAAI,and Joint Council of Allergy and Immunology,for their continued support of parameter development.
The JTF also thank the contributors to this parameter who have been so generous of their time and effort.
Since the last publication of the parameters,there have been several new developments that are discussed in this revision.To accommodate these developments,4new sections have been added to this edition:
1.A discussion on the de?nition of anaphylaxis
2.Controversies and unsettled issues related to anaphylaxis
3.Anaphylaxis in mastocytosis and monoclonal mast cell acti-
vating syndrome(MCAS)
4.Unusual presentations of anaphylaxis
With the addition of the new sections,this revision contains11 chapters dealing with different forms of anaphylaxis in a format the editors believe is unique to all guidelines dealing with this disorder. These sections discuss the general evaluation and management of a patient with a history of anaphylaxis;of?ce management of anaphylaxis;and anaphylaxis to foods,drugs,insect stings,seminal ?uid,exercise,and allergen immunotherapy(AIT).In addition, there are sections on anaphylaxis related to mastocytosis, anaphylaxis occurring in the perioperative period,and unusual manifestations of this disorder.
The document is written so that a reader looking for information can simply choose to review only one of these sections,whereas a reader wanting a comprehensive review could start at the begin-ning of this document and become familiarized with almost all areas of this disorder that are of clinical importance.This format inherently results in some repetition and,inevitably,in some subtle differences of opinion between authors of each section(all of whom are well-recognized experts in their area of discussion).The editors believe repetition in this way is desirable because this al-
P.Lieberman et al./Ann Allergy Asthma Immunol115(2015)341e384343
the section they choose to read.For example,in several sections, there is a repetitive recommendation to supply patients who are at risk for anaphylaxis with an auto-injector for epinephrine.Thus,the Summary Statements will state this recommendation in several places.The editors believe this is desirable because many readers will choose to read only a single section when looking for infor-mation pertinent to a given patient.
Also,because of this repetition,another issue occurs,namely that of subtle disagreements.For example,some authors might judge that there are different strengths of recommendations or grades of evidence for a similar recommendation.The editors believe this adds rather than detracts from the strength of this document.They have judged that it is important for the reader to know that consensus opinion cannot be reached on all issues relative to anaphylaxis.There is simply not enough evidence in many instances to come to de?nitive conclusions.That is the reason for the addition of a section entitled“Controversies and Unsettled Issues Related to Patients at Risk for or Being Treated for Anaphylaxis.”
Another example in which opinions can vary is in how long a patient should be observed after signs and symptoms of an episode of anaphylaxis have resolved.There is no de?nitive answer to this question and therefore experts might disagree.Such disagreements re?ect differences in experiences and cannot be de?nitively adju-dicated.Therefore,this disagreement has not been discouraged,but rather encouraged,in this document.The editors believe that expression of these subtle differences is healthy and should be left intact.
On occasion,the same or similar tables or statements might be present in2different sections.The editors believe it is important to the reader that each section remains complete for the reader who chooses to read only that particular section.It would be inordi-nately inconvenient for the reader to go back and forth through the document to?nd a given table.
Each section has its own set of references.Thus,as in a textbook, a reference can appear in several places in the text.Because it is important to have each section stand alone as a complete source of information,the editors believe it best for the reader to be able to access the references without having to search through the entire document.
Introduction and Considerations on the De?nition of Anaphylaxis
To fully understand the current debate over the de?nition of the term anaphylaxis and the criteria necessary to establish its diag-nosis,one must understand the history behind the development of the term.
The term was coined in1901by Charles Richet and Paul Portier to describe a phenomenon discovered while experimenting with aqueous glycerin extracts of the sea anemone.
It was their intent to“immunize”dogs to the venom of the sea anemone.In doing so,they found that the“opposite effect”was produced.That is,dogs developed an increased sensitivity to the venom with readministration after a course of“immunization”injections.Because they produced the opposite of their original intent,prophylaxis,they called the phenomenon anaphylaxis(ana being Greek for“against”or“opposite”;phylaxis being Greek for “protection”).1,2
The term anaphylaxis gained rapid clinical recognition,and by 1925Arthur Coca3devoted a chapter to this condition in his immunology text.With the increased use of medications,it became evident that anaphylactic reactions could readily occur in human beings,and in1945Robert Cooke4de?ned anaphylaxis as“a special or particular immunologic type of induced protein(or hapten) sensitivity in man or experimental animals and may properly be
With the discovery of immunoglobulin E(IgE),it became apparent that anaphylactic reactions were in many instances mediated by this antibody.However,not all episodes could be attributed to an IgE-mediated mechanism.Thus,it was realized that the clinical expression characteristic of an anaphylactic episode had more than1mechanism of production,and the term anaphylactoid reaction was introduced to describe events that were clinically similar to but not mediated by IgE.1At that time(the1970s),the de?nition of anaphylaxis became“a systemic,immediate hyper-sensitivity reaction caused by IgE-mediated immunologic release of mediators from mast cells and basophils.”The recognition that non e IgE-mediated mechanisms could produce a clinically similar event spawned the descriptor“anaphylactoid.”Thus,“the term ‘anaphylactoid reaction’referred(and still does refer)to a clinically similar event not mediated by immunoglobulin E.”
There were objections to this terminology,and in2003the World Allergy Organization suggested that the term anaphylactoid be abandoned and all such events,regardless of the mechanism of production,be called anaphylactic episodes.They further suggested that these episodes be divided into immunologic and non-immunologic events.Nonimmunologic anaphylactic events could be considered synonymous with the term anaphylactoid,and the immunologic events were further subcategorized as mediated and not mediated by IgE.5,6However,there are problems with this terminology,and to date,the term anaphylactoid,which had become embedded in the lexicon,remains in use.
Despite this intense and well-meaning debate over the de?ni-tion of anaphylaxis,problems still haunted efforts to?nd a completely acceptable terminology.For example,idiopathic anaphylaxis,which is responsible for a signi?cant number of cases,7 is not easily accounted for when using either of these2currently accepted de?nitions.Therefore,Simons8proposed a separate category that is neither immunologic nor nonimmunologic,but rather“idiopathic.”
With these dif?culties in mind,the National Institute of Allergy and Infectious Disease(NIAID)and the Food Allergy and Anaphy-laxis Network(FAAN)and Food Allergy Research and Education assembled experts from multiple specialties including allergists and immunologists,emergency department physicians,intensive care physicians,pediatricians,and internists to establish clinically rele-vant criteria de?ning this condition that would be acceptable not only to the allergy community but also to all physicians managing this disorder.The results of this symposium were published in preliminary form in20059and in a more re?ned version in2006.10 The“de?nition”derived by this panel has been used to discern when an injection of epinephrine is indicated for the management of a patient exhibiting signs and symptoms of an anaphylactic event. Controversy arose over the“de?nition”as discussed in a publication sponsored by the World Allergy Organization.3
Their critique of the NIAID/FAAN document was based on the implication that the criteria for anaphylaxis developed by Cox et al11 might exclude patients with clinical manifestations expressed by a single system only(eg,hives alone)after exposure to a likely allergen.Thus,a patient receiving immunotherapy who developed hives alone,using this criterion,might be excluded from the administration of epinephrine.It should be noted that the“2-system”expression of symptoms developed by the NIAID/FAAN study group was derived by compromise:“For some participants, the primary concern was that a simple clinical de?nition could not include all subjects with anaphylaxis(ie,that it would have less than 100%sensitivity);whereas for others,the more sensitive de?nitions came with an unacceptably high number of false-positive results(ie, the risk of calling mild-allergic reactions‘anaphylaxis’).”12 Realizing this,the criteria established by Sampson et al9 added a caution as follows:“Other presentations may also indi-
P.Lieberman et al./Ann Allergy Asthma Immunol115(2015)341e384 344
caveat appeared in the preliminary report published in2005.In the second,re?ned document,published in2006,10another caveat was added:“There will undoubtedly be patients who present with symptoms not yet ful?lling the criteria of anaphy-laxis,yet in whom it would be appropriate to initiate therapy with epinephrine,such as a patient with a history of near fatal anaphylaxis to peanut who ingested peanut and within minutes is experiencing urticaria and generalized?ushing.”10Thus,it can be seen that this document did recognize the need for the administration of epinephrine in a patient who was exposed to a likely allergen who experienced only a single-system(eg,cuta-neous)manifestation of symptoms.In addition,the criteria used by the NIAID/FAAN workshop to diagnose anaphylaxis have been shown to be useful in an emergency department setting to accurately establish a diagnosis of anaphylaxis.12They were found to have a sensitivity of96.7%and a speci?city of82.4%and demonstrated a positive predictive value of68.6%and a negative predictive value of98.4%.
Controversies and Unsettled Issues Related to Patients at Risk for or Being Treated for Anaphylaxis
The practice parameters developed by the JTF are evidence-based documents that recommend diagnostic and treatment ap-proaches for a given disease state.However,in many instances, evidence on which to base such recommendations is lacking. Therefore,in some cases in which evidence is lacking,recommen-dations for management are based on expert opinion and might encourage an individual physician or other health care provider discretion within a framework of different options.These instances can generate controversy that lead to uncertainties in the approach to patient management.Speci?c issues in regard to the manage-ment of anaphylaxis that meet this description will be discussed in this section.This section is intended to offer evidence-based data on both sides of controversial issues where possible.
However,for issues where there is a lack of high-quality evi-are management issues pertaining to anaphylaxis for which de?nitive recommendations cannot be made.The intent herein is to clarify the source of controversies and present available options to assist the reader in making decisions.Where possible,data relevant to these issues are discussed with consideration of the pros and cons of different management strategies.In the absence of high-quality evidence,management decisions rely to a greater extent on physician or other health care provider experience and patient circumstances.Where appropriate,patients should be given the opportunity to express their values and preferences and participate in the medical decision-making process.
1.Should patients receiving subcutaneous immunotherapy
(SCIT)be prescribed auto-injectable epinephrine(AIE)?
This issue arises because it has been shown that anaphylactic reactions to SCIT can occur after the suggested30-minute wait period.1
Given this observation,it might stand to reason that all patients receiving SCIT should receive a prescription for epinephrine. However,there are other factors to be considered.These include the additional cost and the practicality of patients keeping the injector with them.
For these and other reasons,there is no de?nitive recommen-dation as to whether an auto-injector should be prescribed.In fact, according to the limited available data,there are great variations in practice as to what percentage of allergists and immunologists prescribe epinephrine in this setting.According to a survey,213.5% of allergists and immunologists do not prescribe an AIE for their patients on immunotherapy,33.3%prescribe it to all of their pa-tients on immunotherapy,and52.7%risk stratify their patients by disease severity,history of reactions,and type of immunotherapy. With this degree of variance in practice,it is obvious that there is no consensus of opinion on this issue.
The decision as to whether to prescribe epinephrine in this instance thus remains at the discretion of the physician.
2.Should individuals with large local reactions to insect stings
be given an AIE?
Five present to10%of patients experiencing large local reactions are at risk for a systemic reaction(SR).3e6In the most recent Practice Parameter on Stinging Insect Hypersensitivity,3the decision to prescribe an AIE is left to the discretion of the physician caring for the patient.Providing injectable epinephrine to patients who have a history of large local reactions for use if a subsequent SR occurs is usually not necessary but might be considered if it provides reas-surance to the patient.This decision and the physician’s judgment might be in?uenced by factors such as the potential risk of being stung,personal health issues(eg,the presence of cardiovascular disease),and the individual patient’s preference.The question is,of course,Is a5%to10%risk suf?cient to justify the additional cost,and would it be practical to expect a patient who has never experienced an SR to keep an automatic epinephrine injector on their person?
There are no data to assist in answering this question and thus the choice is left to physician discretion with patient input after consideration of bene?t and burden.
3.Should patients with oral allergy syndrome(fruit-pollen
syndrome)be given an AIE?
The oral allergy syndrome is an IgE-mediated condition that
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J Allergy Clin Immunol.2012;129:748e752.
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anaphylaxis in patients with oral allergy syndrome is unknown,but in a review of multiple studies,it was estimated that the incidence ranges from2%to10%of patients.7However,in a survey of allergists and immunologists,20%of allergists reported that some of their patients did develop systemic symptoms.Thirty percent never prescribed an AIE and3%always did.The remainder prescribed an AIE based on the nature of the patient’s symptoms.8Some author-ities cite features that might increase the risk for a systemic event and thus affect the decision to prescribe an AIE.9These include:
A.A past SR
B.Reaction of any severity to cooked plant food.
C.An established allergy to peanut,tree nuts,or mustard
D.Reactions to particular foods if practicing in an area where that
food is associated with a severe reaction,such as peach or apple in Mediterranean countries
E.A pharyngeal anatomy that might predispose to severe
obstruction even with a mild degree of pharyngeal(laryngeal) swelling,such as large tonsils or a large tongue
F.Patients who have reported dysphagia or signi?cant throat
discomfort during previous reactions
It is clear that these recommendations are derived from reasonable conclusions based on experience and clinical judgment. At this point,there is no consensus on this issue.Therefore,the choice is left to physician discretion,and patients should be given the opportunity to express their values and preferences and participate in the medical decision-making process.
4.Should patients on angiotensin-converting enzyme(ACE)
inhibitors be excluded from immunotherapy to hymenoptera venom?
Although there is some suggestion to the contrary,10there is evidence in the published literature that ACE inhibitors might be a risk factor for an increase in incidence and severity of anaphylaxis to hymenoptera stings and venom immunotherapy(VIT).11e14 There is a warning in the package insert of venom extracts that taking an ACE inhibitor can predispose to an SR during VIT.Because patients who are taking these drugs often cannot discontinue them without risk of cardiovascular or renal problems,this issue in a patient with hymenoptera sensitivity undergoing immunotherapy presents a common and important concern.
The issue can be approached only by analyzing the risk-to-bene?t ratio for each patient,and the decision as to whether to discontinue these drugs is up to the discretion of the allergist in discussion with the other involved consultants(cardiologists,nephrologists).
5.Should a child who develops a contact urticarial reaction on
the face from a food allergen be supplied an AIE?
A few years ago,the Food and Drug Administration’s approved indication for the prescription of an automatic epinephrine injector was changed from a patient who had experienced an episode of anaphylaxis to an individual who is at increased risk for an episode of anaphylaxis.Thus,a child who has experienced contact urticaria to,for example,egg might qualify to receive an automatic epinephrine injector.However,the risk of anaphylaxis in this sit-uation has not been quanti?ed.
It has been documented that automatic epinephrine injectors are often under-prescribed in children with food allergy and anaphylaxis.15e17However,it also has been argued that because the risk of a fatal reaction to food,especially in preschool children,“is increased signi?cantly,it is“important to provide a perspective on the risk of death from food-induced anaphylaxis and use‘risk fac-tors’to assist in making the decision as to whether or not an AIE is indicated rather than prescribing them‘carte blanche.’”18 In keeping with this opinion,it might be reasonable to use risk factors to assist in the decision to prescribe an AIE.Some risk factors that might increase the risk for or severity of an anaphylactic event in a child demonstrating contact urticaria to food have been iden-ti?ed.These include the presence of allergy to peanuts or tree nuts, asthma,and IgE-mediated sensitivity to multiple allergens.19,20In addition,the risk of an SR,but not its severity,can further be assessed by quantitating the size of the skin test reaction and by the quantitative determination of serum-speci?c IgE.21
Despite these observations,there is great variation in how physicians manage food allergy in children.22Speci?cally,there does not appear to be a consensus regarding the use of an AIE in children with contact urticaria to foods,and thus the decision is left to the discretion of the physician.
6.Should a patient presenting with mild systemic symptoms
involving at least1system(eg,urticaria with mild gastroin-testinal cramping)be treated with antihistamines and/or corticosteroids and observed rather than given epinephrine?
Anaphylactic fatalities are rare,23,24and in the vast majority of instances,patients will do well.Nevertheless,fatalities do occur and reactions presenting with mild symptoms can rapidly progress to cardiovascular and respiratory arrest.In addition,it is improb-able that patients experiencing anaphylactic events would be protected by antihistamine or corticosteroid because the onset of pharmacodynamic activity of these2classes of drugs is too slow to prevent cardiorespiratory arrest.For example,fexofenadine(180 mg)given by mouth failed to exhibit any inhibitory effect on histamine-induced wheal and?are at30minutes and did not exhibit a50%suppression of wheal and?are until more than100 minutes after administration.Diphenhydramine at50mg admin-istered intramuscularly did not show a50%decrease in skin test expression until51.7minutes,and diphenhydramine at50mg administered orally did not demonstrate such a decrease until79.2 minutes after administration.25As noted,these times are insuf?-cient to prevent cardiorespiratory arrest or death.In the largest study of anaphylactic deaths to date,it was found that the median time to respiratory or cardiac arrest was30minutes for foods,15 minutes for venom,and5minutes for iatrogenic reactions.26In another study of fatalities,death occurred within60minutes in13 of25cases.27Thus,based on their pharmacodynamics activity, antihistamines or corticosteroids would not prevent cardiorespi-ratory arrest or death in many instances.In addition,antihista-mines would only antagonize the effect of histamine,whereas there is ample evidence that other mediators such as platelet activating factor and kinins are associated with severe and potentially fatal reactions.28,29Unfortunately,at the initiation of symptoms,often one cannot predict whether an episode will rapidly progress.30 Because the clinical course of anaphylaxis can be unpredictable, prompt and early use of epinephrine should be considered even with mild symptoms or single-system involvement.
7.Should an elderly patient with hypertension and/or arterio-
sclerotic heart disease who is at risk of an episode of anaphylaxis be given an AIE?Also,should such a patient experiencing an episode be treated with epinephrine?
The pharmacologic effects of epinephrine are well known,and
P.Lieberman et al./Ann Allergy Asthma Immunol115(2015)341e384 346
rate,and force of contraction is bene?cial in the treatment of anaphylactic episodes.However,these effects can be detrimental in a person with arteriosclerotic heart disease and/or hypertension. The administration of epinephrine to treat episodes of anaphylaxis has been associated with the occurrence of myocardial infarction and acute coronary syndrome on rare occasions.31,32However,this might be due to“guilt by association”rather than cause and effect because there are abundant mast cells in the human heart and the mediators of anaphylaxis can produce coronary artery vasospasm, and infarction can occur as part of the natural history of an anaphylactic episode.33,34
Thus,physicians and other health care providers faced with treating anaphylaxis in a patient with cardiovascular disease are presented with a dilemma.However,there is no absolute contraindication to the administration of epinephrine as clearly stated in the Food and Drug Administration package insert for AIE. This includes patients with acute coronary syndrome,and although the risk-to-bene?t ratio needs to be assessed with care in such patients,it usually favors the administration of epinephrine. Moreover,cardiovascular disease does not“forbid”the use of epinephrine in the treatment of anaphylaxis.Nonetheless,there are no means by which data can be collected to support this statement because clearly the problem does not lend itself to experimental analysis.
8.Auto-injectors are available in0.3-mL(0.3-mg)and0.15-mL
(0.15-mg)doses.The package insert states that the0.3-mg
epinephrine dose is“intended for patients who weigh15 to30kg(33e66pounds).”In a child weighing less than15 kg,should an automatic injector be used or should the caregiver be instructed to maintain an ampule or a multi-dose vial and a tuberculin syringe to be used to treat events?
Although there are no clear-cut answers to this question, dosing mistakes are not uncommon when epinephrine is administered by syringe,and nonmedical personnel can have dif?culties using this method.35e37Thus,an automatic epinephrine injector is clearly the preferred means of achieving an accurate dose.
Also,it is important to note that the optimal dose of epinephrine is unknown.There have been no published dose e response studies documenting that the suggested dose of0.01mg/kg is indeed the “correct dose,”and the origin of this suggested dosage regimen could not be found.In fact,before the advent of currently available automatic epinephrine injectors,the recommended doses of epinephrine varied considerably.In the early epinephrine litera-ture,asthma was treated in adults with1-mg doses and in infants weighing25pounds with1/16th of the adult dose.38Variations of this dose ranging from0.2to0.5mg were recommended for the treatment of anaphylaxis as late as1978.39There have been commercially available preloaded epinephrine injectors?lled with a dose of0.5mg for the administration to adults,and this dose was well accepted as optimal for the treatment of anaphylaxis until the advent of automatic injectors.Thus,the actual optimal dosing regimen is unknown.
With these observations in mind,it would seem prudent to consider prescribing an automatic epinephrine injector in children who are experiencing an anaphylactic event who weigh less than 33pounds.
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induced cutaneous responses by oral and intramuscular diphenhydramine and oral fexofenadine.Ann Allergy Asthma Immunol.2008;100:452e456.IIb.
[26]Pumphrey RS.Lessons for management of anaphylaxis from a study of fatal
reactions.Clin Exp Allergy.2000;30:1144e1150.IIIb.
[27]Greenberger PA,Rotskoff BD,Lifschultz B.Fatal anaphylaxis:postmortem
?ndings and associated comorbid diseases.Ann Allergy Asthma Immunol.
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[28]Vadas P,Perelman B,Liss G.Platelet-activating factor,histamine,and tryptase
levels in human anaphylaxis.J Allergy Clin Immunol.2013;131:144e149.IIb.
[29]Sala-Cunill A,Bj?rkqvist J,Senter R,Guilarte M.Plasma contact system acti-
vation drives anaphylaxis in severe mast cell e mediated allergic reactions.
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[30]Sampson HA,Mendelson LM,Rosen JP.Fatal and near fatal anaphylactic re-
actions to food in children and adolescents.N Engl J Med.1992;327:380e384.IIIb.
[31]Shaver KJ,Adams C,Weiss SJ.Acute myocardial infarction after administra-
tion of low-dose intravenous epinephrine for anaphylaxis.CJEM.2006;8: 289e294.IIIb.
[32]Rubio Caballero JA,Oteo Domínguez JF,Maicas Bellido C,et al.An adrenaline-
induced vasospasm as the form of presentation of variant angina.Rev Esp
P.Lieberman et al./Ann Allergy Asthma Immunol115(2015)341e384347
Executive Summary
This executive summary has been developed from the summary statements at the beginning of each section of the document.These summary statements contain the most important points from their respective sections as judged by the authors of each.The reader is referred to the full section for discussion and references pertaining to the points summarized in the Executive Summary.
Any patient who has experienced an episode of anaphylaxis should be evaluated to determine the causative agent.When the cause is not readily identi ?ed,the patient should be referred to an allergist or immunologist to conduct this evaluation.Any patient who has experienced anaphylaxis when the cause is not completely avoidable or cannot be determined should be supplied with an AIE and should be instructed in the use of this device and told to keep their AIE with them at all times.The patient should be taught to recognize the signs and symptoms of anaphylaxis and when to administer the injection and be given an anaphylaxis action plan.Because anaphylactic episodes might require more than 1dose of epinephrine,all patients should carry 2AIEs.
The patient should be instructed to wear and carry identi ?cation denoting the patient ’s condition (eg,MedicAlert,2193West Chester Pike,Broomall,PA 19008).
Individual risk factors should be taken into consideration.These include age,activity,occupation,hobbies,residential conditions,and access to medical care.It is important to consider the patient ’s level of anxiety,and attempts should be made to have patients gain con ?dence in their ability to treat any future event.
Pharmacologic prophylaxis such as glucocorticosteroids and antihistamines can be used in select situations such as in the pre-vention of anaphylaxis to drugs or biologic agents (eg,radiocontrast material [RCM])or to prevent recurrent episodes of idiopathic anaphylaxis.It should be recognized that,especially in adults,a very signi ?cant portion of patients have anaphylactic episodes for which no cause can be determined.Desensitization procedures to perform the temporary induction of tolerance also can be used in certain situations (eg,penicillin allergy).
Patients should be educated about the presence of hidden al-lergens (eg,tree nuts in pie crust)and should be informed about cross-reactivity between allergens in drugs (eg,various b -lactam antibiotics)and foods (eg,lentils and peanuts).
Any patient subject to episodes of anaphylaxis should be counseled regarding the use of certain medications that could worsen any future event or complicate therapy (eg,b -adrenergic blockers).
The appropriate treatment of an acute event that might occur in a medical of ?ce requires planning and preparation.Plan for an appropriate of ?ce response to anaphylaxis by (1)educating staff and patients;(2)preparing an anaphylaxis emergency cart;and (3)developing an of ?ce action plan for anaphylaxis management to primary providers)to recognize and monitor the patient for the early signs and symptoms of anaphylaxis in preparation for epinephrine administration.
At the onset of anaphylaxis,(1)administer epinephrine intra-muscularly in the mid-outer thigh;(2)remove the inciting allergen,if possible (eg,stop an infusion);(3)quickly assess airway,breath-ing,circulation,and mentation,and summon appropriate assis-tance from staff members;and (4)start,if needed,cardiopulmonary resuscitation and summon emergency medical services (EMS).Epinephrine should be administered and then immediately thereafter EMS should be noti ?ed for patients having severe anaphylaxis and/or patients not responding to epinephrine.Recognize that more than 1injection might be necessary in some patients.
The patient should be placed in a supine position,unless res-piratory compromise contraindicates it,to prevent or counteract potential circulatory collapse.Pregnant patients should be on their left side.For maintaining hemodynamic stability,intravenous ac-cess is essential.Oxygen should be administered to patients with any respiratory dif ?culty.
There should be a rapid and ongoing assessment of the patient ’s airway status.Airway patency should be maintained using the least invasive but effective method (eg,bag-valve-mask).Intravenous ?uid replacement with normal saline is indicated for patients with circulatory collapse and for patients who do not respond to intra-muscular epinephrine.Hypotension of any degree should prompt the administration of intravenous ?uid.
For respiratory symptoms not responding to epinephrine,nebu-lized b 2-agonists such as albuterol should be administered.In pa-tients who are receiving b -adrenergic blocking agents,glucagon should be administered if there is a failure to respond to epinephrine.H 1and H 2antihistamines or corticosteroids can be given as adjunctive therapy after the administration of epinephrine but are not indicated as initial treatment for anaphylaxis in place of epinephrine.Consider these agents as optional therapy.
The treatment and duration of the event should be individual-ized based on the result of constant monitoring.Longer periods of observation are indicated for patients who have a history of risk factors for severe anaphylaxis such as asthma,previous biphasic reactions,or a previous protracted anaphylactic event.Patients with these risk factors who do not respond to treatment should be observed for at least 4to 8hours.On release from treatment,all patients should be prescribed an AIE,given an anaphylaxis action plan,and educated in the symptoms that might indicate another reaction.
Foods are the most common cause of anaphylaxis,followed by drugs.The most common foods to cause anaphylactic events are peanuts,tree nuts,?sh,shell ?sh,milk,and egg,but any food can produce a reaction.Thus,food should be considered a possible cause of an anaphylactic reaction in any patient experiencing an event.In addition,anyone who has experienced an anaphylactic event should be considered for allergy testing to foods.If this event is delayed several hours after a meal,one also should consider testing for IgE antibodies against galactose-a -1,3-galactose (alpha-gal).This is particularly true if there is a history of tick bites or if the preceding meal consisted of mammalian meat.This oligosaccharide allergen is expressed on tissues of all nonhuman mammals.Pa-tients who have IgE anti e alpha-gal should be advised to avoid all mammalian meats.
It is not possible to predict the severity of any future event based on the severity of past https://www.doczj.com/doc/3c11467090.html,d events can be followed by life-threatening events.There is no current diagnostic test that will adequately predict the severity of the next episode of anaphylaxis.Some patients are at high risk for fatal food-induced anaphy-laxis.Risk factors include (1)adolescents,(2)patients with a history [33]Triggiani M,Patella V,Staiano RI,Granata F,Marone G.Allergy and the car-diovascular system.Clin Exp Immunol .2008;153(suppl 1):7e 11.IIIb .
[34]Ridella M,Bagdure S,Nugent K,Cevik C.Kounis syndrome following beta-lactam antibiotic use:review of literature.In ?amm Allergy Drug Targets .2009;8:11e 16.IIIb .
[35]Kanwar M,Irvin CB,Frank JJ,Weber K,Rosman H.Confusion about
epinephrine dosing leading to iatrogenic overdose:a life-threatening prob-lem with a potential solution.Ann Emerg Med .2010;55:341e 344.IIIb .
[36]Kaji AH,Gausche-Hill M,Conrad H,et al.Emergency medical services system
changes reduce pediatric epinephrine dosing errors in the prehospital setting.Pediatrics .2006;118:1493e 1500.IIIb .
[37]Simons FER,Chan ES,Xiaochen G,Simons KJ.Epinephrine for the out-of-hospital
(?rst-aid)treatment of anaphylaxis in infants:Is the ampule/syringe/needle method practical?J Allergy Clin Immunol .2001;108:1040e 1044.IIIb .
[38]Cooke RA .Allergy in Theory and Practice .Philadelphia,PA:WB Saunders;
1947:159.IIIb .
[39]Orange RP,Donsky GJ.Anaphylaxis.In:Middleton E,Reed CE,Ellis EF,eds.
Allergy:Principles and Practice .St Louis,MO:CV Mosby;1978:570.IIIb .
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348
patients with a history of asthma,or(5)those presenting with the absence of cutaneous symptoms.
The diagnosis of food-induced anaphylaxis should be based on signs and symptoms in association with likely or known exposure to a food allergen.Events mimicking anaphylaxis also can occur after the ingestion of food.For example,the ingestion of“spoiled”scombroid?sh,owing to the high content of histamine,can pro-duce reactions mimicking an anaphylactic event.During such events,the serum tryptase will not be elevated,but24-hour urinary histamine can be increased.
Avoidance of the causative food and foods that might cross-react with the culprit is the mainstay of long-term treatment of food-induced anaphylaxis.At this time,immunotherapeutic treatments (eg,desensitization)remain a research tool.Currently,there is inadequate evidence available to analyze the long-term therapeutic bene?t compared with risk.
As with all other causes of anaphylaxis,patients who have experienced an episode of anaphylaxis to foods should be supplied with AIEs,instructed in their use,taught the signs and symptoms of anaphylaxis,and given an anaphylaxis action plan.
Medications rival food for the most common cause of anaphy-laxis.The most common classes of drugs producing anaphylaxis are (1)antibiotics,especially b-lactam antibiotics,and(2)nonsteroidal anti-in?ammatory drugs(NSAIDs).Skin tests can be helpful in evaluating some drugs.When penicillin is suspected,skin tests can be performed to the major allergen(benzylpenicilloyl polylysine)in addition to penicillin G as a surrogate for the minor determinant allergens.The negative predictive value of such testing is95%to99%. Patients who are allergic to penicillin have a very low risk of reacting to cephalosporins,but life-threatening events have occurred when patients allergic to penicillin have been treated with cephalosporins.
Vancomycin can produce manifestations similar to anaphylaxis. However,these reactions are not mediated by IgE and usually can be prevented by administering the drug through a slow intravenous infusion.
Anaphylactic reactions to omalizumab can be delayed in onset and progressive.Therefore,patients receiving this drug should be observed for2hours after the?rst3injections and30minutes after subsequent injections.Any patient receiving omalizumab should be prescribed an AIE,taught the signs and symptoms of anaphylaxis, and given an anaphylaxis action plan.The patient should carry the AIE to the of?ce when receiving the injection and should keep it on his or her person for24hours after the injection.
Skin testing also can be helpful in patients who have developed anaphylaxis owing to biologic agents.In patients who have had anaphylaxis to a biologic agent,if no therapeutic alternative exists, then consider rapid desensitization to induce temporary tolerance, recognizing that repeat desensitizations might be necessary depending on the interval between infusions.
For patients who have experienced an anaphylactic reaction to RCM,if future administration is needed,then use a lower osmo-lality preparation and premedicate patients with prednisone and antihistamines at the appropriate times.
Insect sting reactions also are common causes of anaphylactic events.Patients experiencing anaphylactic reactions to an insect sting should undergo skin testing to venom if the insect was a “?ying hymenoptera”and to whole-body extract if it was a?re ant, but patients experiencing only large local reactions and children with only mild cutaneous SRs need not be tested.These groups generally do not require venom testing or VIT because the inci-dence of anaphylaxis on repeat sting is low(5e10%).
Any patient experiencing an anaphylactic event to a hymenop-tera sting should have a baseline serum tryptase performed because such patients are at risk of having systemic mastocytosis(SM).
Venom skin tests are preferred because they are the most sen-procedure.Patients who have had an anaphylactic reaction to a sting but do not demonstrate a positive skin test reaction should have in vitro tests performed.
The level of skin test or in vitro test reactivity does not reliably predict the severity of a future sting reaction,and the diagnosis cannot be made based only on skin testing or in vitro testing.The history is essential because of asymptomatic venom sensitization. Such asymptomatic sensitization occurs in up to25%of adults.
Venom immunotherapy is recommended for patients with systemic sensitivity to?ying hymenoptera because this treatment is highly effective(80e98%).The treatment of?re ant hypersensi-tivity is conducted with whole-body extracts.They appear to pro-vide adequate allergen concentration for reasonable ef?cacy.
Anaphylaxis during the perioperative period is unique in its characteristics.It can be dif?cult to diagnose because of the affected patient’s inability to communicate,the skin is covered,and there is a decreased occurrence of skin manifestations.In addition,deter-mining the causative agent is dif?cult because numerous medica-tions are often administered simultaneously.
The most frequent causes of these events are neuromuscular blocking agents and antibiotics.The b-lactam antibiotics are the most frequent class involved.However,other agents can be responsible.These include barbiturates,opioids,supravital dyes, latex,and transfusions.Skin testing and in vitro testing can be helpful in discerning the responsible agent.Validated skin tests and/or in vitro techniques are available for several drugs,including neuromuscular agents,latex,and b-lactam antibiotics.
Seminal?uid anaphylaxis is relatively rare but a signi?cant problem for those affected.Seminal?uid anaphylaxis is diagnosed based on history.An event occurring during or immediately after coitus with classic anaphylactic manifestations suggests the diag-nosis.Skin testing with fresh whole human seminal plasma or its fractions can be performed.The specimen should be obtained from the male partner.Other underlying causes,such as allergy to nat-ural rubber latex condoms or drugs passively transferred through seminal plasma,also should be considered.
Patients with postcoital local reactions to human seminal plasma can be treated by intravaginal graded challenge to dilutions of whole seminal?uid or by systemic desensitization to relevant seminal plasma proteins.Patients experiencing systemic seminal ?uid plasma hypersensitivity should always have an AIE available and barrier protection should always be used.
The patient with seminal plasma allergy should be informed that that infertility does not appear to be linked to seminal plasma hypersensitivity,and they might be able to conceive by arti?cial insemination with washed spermatozoa.
A cause of anaphylaxis that is often missed is exercise.Patients can experience anaphylaxis owing to exercise of any type,including running,cycling,and resistance exercise.This condition should be distinguished from cholinergic urticaria,which occurs whenever body temperature is elevated.The latter can occur with a hot shower,whereas patients with exercise-induced anaphylaxis(EIA) can tolerate exposure to heat quite well.
In some patients with EIA,cofactors are needed for the event to occur.These cofactors include the ingestion of foods,NSAIDs(espe-cially aspirin),and,rarely,in individuals with atopy,high pollen levels.
Patients who have EIA should avoid exercise in the immediate postprandial period especially if the events have been associated with the ingestion of food.They could undergo skin testing to determine whether a speci?c food is responsible.
It is important to note that these events can be inconsistent in their occurrence.They will not necessarily occur with each exercise regimen.Therefore,exercise challenge testing does not consistently reproduce symptoms and is not necessarily a useful part of the evaluation.Patients with these events should stop exercising
P.Lieberman et al./Ann Allergy Asthma Immunol115(2015)341e384349
can worsen the episode.All patients with this disorder should carry 2AIEs whenever they exercise and should exercise with a partner who can recognize symptoms and administer the epinephrine.
Prophylactic treatment is inconsistently effective and often fails to prevent events.Therefore,such treatment cannot be trusted to eliminate the need for exercising with a partner or carrying an AIE.
Subcutaneous AIT can produce anaphylactic events.Therefore, patients undergoing this treatment should be advised about the risk of immediate and late-onset reactions(beginning after30 minutes).Allergy injection therapy should be administered in a supervised clinic setting staffed by personnel trained in recognition and treatment of anaphylaxis,and the patient should be observed for at least30minutes after the injection.
Most fatal anaphylactic reactions to allergy injections have been reported in patients with uncontrolled asthma.Thus,patients with asthma receiving immunotherapy should have the state of their asthma assessed before each injection.
In patients receiving VIT,ACE inhibitors have been associated with an increased frequency of reactions and should be discontinued (substituted)whenever possible.Beta-adrenergic blocking agents also have been reported to be associated with more severe events and can interfere with the activity of epinephrine.Therefore,their discontinuation(substitution)should be considered.Patients who cannot discontinue b-blockers should be advised of the risks involved and the risk-to-bene?t ratio should be carefully analyzed.
During the past decade,it has been recognized that patients with SM or monoclonal MCAS(MMAS)are at increased risk for anaphylaxis.Thus,any patient with repeated episodes of anaphy-laxis with unknown cause should have a baseline(asymptomatic) serum tryptase assay because an elevated baseline serum tryptase suggests these diagnoses.
In addition,in such patients,a bone marrow biopsy should be considered.The biopsy should be evaluated by immunohisto-chemical staining and tagged antibodies to mast cell tryptase and CD2and CD25should be used to detect their presence on CD117 (KIT)-positive cells.
One should always be aware that anaphylaxis can present with unusual clinical manifestations such as somnolence and chest pain in children,chest pain in adults,and syncope and seizure without any other sign or symptom.
I.Evaluation and Management of Patients with a History of Anaphylaxis
Summary Statement1:Evaluate any patient who has experi-enced an episode of anaphylaxis for which the cause is not readily identi?ed to determine the cause and refer to an allergist or immunologist to conduct this evaluation.[Recommendation;D Evidence]
Summary Statement2:Supply any patient who has experienced an episode of anaphylaxis for which the allergen cannot be easily and completely avoided with an AIE and instructions as to when and how to administer this injector and emphasize that they should carry2AIEs with them at all times.[Strong Recommendation;C Evidence]
Summary Statement3:Instruct the patient to wear and/or carry identi?cation denoting his or her condition(eg,MedicAlert,2193 West Chester Pike,Broomall,PA19008)and give the patient an anaphylaxis action plan.[Strong Recommendation;D Evidence] Summary Statement4:Individualize avoidance measures taking into consideration factors such as the patient’s age,activity,occu-pation,hobbies,residential conditions,access to medical care,and level of personal anxiety.[Recommendation;D Evidence] Summary Statement5:Use pharmacologic prophylaxis such as prevent recurrent anaphylactic reactions to RCM or to prevent idiopathic anaphylaxis).[Recommendation;C Evidence] Summary Statement6:When necessary,induce a temporary tolerance(desensitization)in patients who have experienced anaphylaxis from medications.[Recommendation;C Evidence] Summary Statement7:Educate patients about hidden allergens and cross-reactivity between various allergens and drugs. [Recommendation;C Evidence]
Summary Statement8:Counsel patients at risk for future epi-sodes regarding the use of medications that could worsen an event or complicate therapy(eg,b-adrenergic blockers).[Recommenda-tion;C Evidence]
The care of patients presenting for evaluation and management after an episode of anaphylaxis requires knowledge of the symp-toms,pathophysiology,differential diagnosis,and prevention of anaphylactic episodes.1e90
An algorithm for the evaluation and management of a patient with a history of anaphylaxis is presented in Figure I-1. Performing the History
To interpret the history adequately,it is essential to know the manifestations of anaphylaxis.These manifestations can best be ascertained by a review of published series on the topic.1e13A sum-mary of the signs and symptoms as reported in these series,totaling 1,865patients,is presented in Table I-1.These series include patients of all ages with EIA,idiopathic anaphylaxis,and other causes.The most frequently seen manifestations of anaphylaxis are cutaneous, occurring in62%to90%of reported cases.This?gure differs from that published in previous parameters14based on a recently conducted survey.13In this survey,a lesser incidence of cutaneous manifesta-tions was recorded by patients.Only62%of these patients recalled, based on a telephone survey,cutaneous symptoms.Nonetheless,the absence of cutaneous symptoms speaks against a diagnosis of anaphylaxis but does not rule it out.Severe episodes characterized by rapid cardiovascular collapse and shock can occur without cutaneous manifestations.27e29It might be helpful to better assess the signs and symptoms of the reaction by interviewing friends and/or family members who might have been present during the event.In addition, it is important to note that anaphylaxis can present with unusual manifestations(see Section IX,Unusual Presentation of Anaphylaxis), such as syncope without any further sign or symptom.10In addition, based on studies limited to children,the incidence of cutaneous manifestations in children might be lower.31,53The essentials of the history are listed in Table I-2.
The history and the medical record should include the time of occurrence of the attack,the setting in which it occurred,any treatment required during the episode,and the duration of the episode.A detailed history of all potential causes should be ob-tained.This includes a list of ingestants consumed and/or medi-cations taken within6hours of the event,any sting or bite occurring before the event,and whether the event occurred during exercise.The location(work vs home)and whether the event was related to exposure to heat,cold,or occurred during sexual activity also should be determined.The patient’s atopic state should be noted because food-induced,seminal?uid-related,and idiopathic anaphylaxis episodes are more common in patients with than in those without atopy.In women,the history should include any relationship between the attack and their menstrual cycle.A return of symptoms after a remission should be noted because this could indicate a biphasic reaction,5,32which might require a prolonged period of observation if subsequent events occur.
Differential Diagnosis
The differential diagnosis(Table I-3)must be considered
P.Lieberman et al./Ann Allergy Asthma Immunol115(2015)341e384 350
anaphylaxis.A comprehensive differential diagnoses is presented in Table I-3.Vocal cord dysfunction and panic attacks should be considered in the differential diagnosis.
Special attention in the differential diagnosis should be given to vasodepressor(vasovagal)reactions.Characteristic features of this reaction include hypotension,pallor,weakness,nausea,vomiting, and diaphoresis.Such reactions often can be distinguished from anaphylaxis by a lack of characteristic cutaneous manifestations (urticaria,angioedema,?ush,and pruritus)and the presence of bradycardia during the vasodepressor reaction instead of tachycardia usually seen with anaphylaxis.However,it should be noted that bradycardia can occur during anaphylaxis.14,47This is probably due to the Bezold-Jarisch re?ex,a cardioinhibitory re?ex that has its origin in sensory receptors in the inferoposterior wall of the left ventricle.Unmyelinated vagal C?bers transmit the re?ex.Brady-cardia occurs immediately with a vasodepressor event,but in anaphylaxis,tachycardia often precedes the onset of bradycardia.14,47 Flushing episodes can mimic anaphylactic events.Several drugs and ingestants including niacin,nicotine,catecholamines,ACE in-hibitors,and alcohol can induce?ushing.14,34,47
Other conditions that cause?ushing must be considered, including rosacea,gastrointestinal and thyroid tumors,carcinoid syndrome,pheochromocytoma,hyperglycemia,postmenopausal ?ush,alcohol-induced?ushing,and the“red man syndrome”owing to the administration of https://www.doczj.com/doc/3c11467090.html,boratory studies(Table I-4) can be helpful in establishing the diagnosing the diagnosis.
There is a group of postprandial syndromes that can mimic anaphylaxis,such as monosodium glutamate-induced reactions and reactions to scombroid?sh.The latter is increasing in fre-quency,14,35and because it is due to histamine produced by histidine-decarboxylating bacteria that cleave histamine from his-tidine in spoiled?sh,the symptoms can be identical to those that occur in anaphylaxis.However,the cutaneous manifestation might be more of a?ush(sunburn-like)than urticaria.Symptoms might affect more than1individual because anyone eating the?sh can be affected.Serum tryptase levels are normal.
Not infrequently,nonorganic disease can mimic anaphylactic ep-isodes.Such events can be involuntary(panic attacks),undifferenti-ated somatoform anaphylaxis,14,56,76,77and vocal cord dysfunction syndrome.On rare occasions,events can be self-induced as a variation of Munchausen syndrome.Undifferentiated somatoform anaphylaxis describes the presentation of manifestations mimicking anaphylaxis but without objective con?rmatory?ndings.Like other somatoform disorders,this condition is related to psychological problems.
There are other conditions that can mimic anaphylaxis.For example,patients with hereditary angioedema often can have evanescent cutaneous?ndings that can be confused with urticaria. Other rare disorders such as capillary leak syndrome and para-doxical pheochromocytoma also must be considered under the differential diagnosis.
Using Tests and Procedures to Establish the Diagnosis of Anaphylaxis and its Cause
Laboratory tests useful in establishing the diagnosis and cause of an anaphylaxis are listed in Table I-4.
The most useful laboratory test to con?rm a diagnosis of anaphy-laxis at the time of an event is probably serum tryptase.However,at least in1study,38determination of plasma histamine was more sen-sitive than serum tryptase.In this study,elevations of plasma hista-mine were observed in42of97patients,whereas only20had elevations of tryptase.Patients with elevated histamine were more likely to have urticaria,more extensive erythema,abnormal abdominal ?ndings,and wheezing.The advantage of measuring24-hour urinary histamine metabolites rather than plasma histamine is the fact that by to normal because they remain elevated for only30to60minutes.This is the reason that tryptase is measured in most instances rather than plasma histamine.Tryptase levels peak60to90minutes after the onset of symptoms and remain elevated for at least5hours.
Total tryptase levels can be elevated in conditions other than mastocytosis and anaphylaxis,such as acute myelocytic leukemia, hypereosinophilic syndrome associated with the F1P1L1-PDGFRA mutation,myelodysplastic syndromes,end-stage renal disease with endogenous stem cell factor elevation,and acquired C1 esterase de?ciency in association with non-Hodgkin lymphoma.36 Prostaglandin determinations are commercially available and can be of value in diagnosing anaphylactic events.57In a study of patients with SM who experienced anaphylaxis,it was found that mast cell activation could be manifested by a selective excessive release of prostaglandin D2.Of note is that these patients respon-ded to the administration of aspirin but not to antihistamines.57 Further studies can be obtained should other diagnoses be suspected.For example,?ushing without pruritus or urticaria suggests carcinoid syndrome or the presence of a vasointestinal polypeptide tumor or even perhaps a paradoxical reaction to a pheochromocytoma.
In this instance,the measurement of neuropeptides can be helpful.Chromogranin A is a precursor to several functional pep-tides including pancreastatin.It is elevated in carcinoid syndrome and can be elevated in pheochromocytoma.
Other neuropeptides can be elevated in gastrointestinal-secreting vasointestinal polypeptide tumors.Such tumors produce abdominal cramping pain,diarrhea,nausea,and intermittent episodes of ?ushing.Measurement of neuroendocrine hormones including vas-ointestinal polypeptide,neurokinin A,substance P,pancreastatin, and others is readily available.In addition,computed tomography, magnetic resonance imaging,and single-photon emission computed tomography can be helpful.These can be assisted by the adminis-tration of octreotide or pentetreotide,which binds to tumors, enhancing their detection.59To diagnose a pheochromocytoma,24-hour urinary catechol,serum catechol,and plasma-free meta-nephrine(the test of choice)levels are measured.60
Tests to establish the cause of an event include skin and in vitro tests for serum speci?c IgE to foods and drugs,serum IgE to alpha-gal,baseline serum tryptase,24-hour urinary histamine metabo-lites,prostaglandin D2,oral challenges,and,in some cases,a bone marrow determination.
On occasion,fresh-food“prick-to-prick”testing is more sensi-tive than testing with commercial extracts and has been used to identify a food culprit undetected by testing with commercial extracts.
Recent advances that have altered the approach to the use of the laboratory to establish a causative agent are the discovery of the role of alpha-gal and the importance of mastocytosis and mast cell activating disorders as causes of anaphylactic events.
A novel IgE antibody to a mammalian oligosaccharide has been discovered that is associated with2distinct forms of anaphylaxis, an immediate onset of an event to cetuximab and a delayed onset of anaphylaxis,usually occurring3to6hours after the ingestion of mammalian food products(eg,beef and pork).61This oligosaccha-ride,alpha-gal,is a major blood group substance of nonprimate mammals and a well-known target of IgG antibodies that are pre-sent in the serum of all immune-competent individuals.Sensiti-zation appears to occur through tick bites.The predominant cause of these IgE antibodies in the United States is bites from the Lone Star tick(Amblyomma americanum),but cases have been reported from other countries from other species.It is interesting that this IgE antibody to alpha-gal cross-reacts with cat and dog but does not appear to pose a risk for asthma.However,it can impair diagnostic testing in some situations.Of importance is that IgE anti e alpha-gal
extracts of mammalian meat,but there is a commercially available test to detect serum speci?c IgE anti e alpha-gal.A signi?cant number of previously considered idiopathic anaphylactic events are due to this mechanism.61
Alpha-gal is a suspected culprit in any case without known cause,especially in events occurring a few hours after eating, particularly those beginning in the early morning hours.
The realization that mastocytosis and mast cell activating dis-orders can be responsible for episodes previously thought of as idiopathic has altered the approach to patients.The seminal article establishing a relation between mastocytosis and mast cell acti-vating disorders was published in Blood in2007.62In this article, patients with idiopathic anaphylaxis had a clonal disorder of mast cells.The investigators reported on12patients with idiopathic anaphylaxis who did not have characteristic bone marrow biopsy results characteristic of mastocytosis.That is,the biopsy results did not meet the criteria established by the World Health Organization (WHO)cited as necessary to establish a diagnosis of this disorder (Table I-5).However,some patients did demonstrate at least1minor criterion for mastocytosis.Some showed positivity for the816D>V mast cell activating mutation.Since that publication,other studies con?rming this observation have been published.These observa-tions have prompted a proposed change in the nosology and clas-si?cation of anaphylactic events.63The new proposed nosology was derived at an international conference convened to establish consensus-based,evidence-supported diagnostic criteria for MCASs.
This proposed nosology suggests that mast cell activating con-ditions be classi?ed into3distinct categories:
1.Mastocytosis and mast cell activating disorders
2.IgE-mediated anaphylactic events
3.Idiopathic anaphylactic episodes
Mast cell activating disorders resemble mastocytosis and can cause anaphylaxis but lack suf?cient bone marrow?ndings to make a diagnosis of mastocytosis according to the criteria established by the WHO64(Table I-5).Such patients exhibit some bone marrow ?ndings seen in mastocytosis and can have gain in function mu-tations in c-kit.The diagnostic criteria for a diagnosis of a mast cell activating disorder63are listed in Table I-6.
The importance of establishing that mastocytosis and mast cell activating disorders can be the cause of idiopathic anaphylaxis is the fact that mast cell activating disorders can,on occasion,be controlled with tyrosine-kinase inhibitors and that,in the future,a tyrosine-kinase inhibitor that can control SM might be developed.
Baseline elevations in serum tryptase,plasma histamine,24-hour urinary histamine metabolites,or prostaglandin D2suggest these conditions.The traditional cutoff value of20ng/mL used to establish an elevated level of serum tryptase might be too high. Mastocytosis and mast cell activating disorder can be present in patients with lower levels of serum tryptase.A study of patients who had hymenoptera anaphylaxis found that a level of11.7ng/mL was a marker for underlying mastocytosis.65
A screening test performed on blood to detect the816V muta-tion can establish mastocytosis in most cases,23,24but the most de?nitive way to make a diagnosis of mastocytosis is to obtain a bone marrow biopsy specimen.
Thus,one is faced with the decision of whether to perform a bone marrow biopsy examination in patients in whom no cause for anaphylaxis has been determined.When to do so remains a cause of debate.However,there is growing importance regarding making such a diagnosis because some MCASs and some cases of masto-cytosis that are negative for816V can be treated with tyrosine-kinase inhibitors.22,25,26
To con?rm a diagnosis of anaphylaxis in patients who have stating that measurement of serum tryptase,plasma histamine,24-hour urinary histamine metabolites,and perhaps prostaglandin D2, depending on the capabilities of the emergency department, should be obtained.
It has been proposed that elevations of postmortem serum tryptase be used to establish anaphylaxis as a cause of death.42 However,it should be clearly noted that postmortem elevation of serum tryptase concentrations is not a speci?c?nding and there-fore cannot be considered diagnostic of an anaphylactic death. There are reports of non-anaphylactic deaths with elevated post-mortem serum tryptase levels.43e45Thus,the presence of an elevated postmortem tryptase level cannot be considered patho-gnomonic for a death owing to anaphylaxis.Moreover,the absence of an elevated serum tryptase postmortem cannot be considered suf?cient to rule out anaphylaxis as the cause of death.In patients with a possible anaphylactic reaction to food,leftover or vomited food might be useful as a source of antigen for the creation of an in vitro test reagent.
Prevention and Management of Further Episodes
Some anaphylactic reactions are so severe that treatment is unsuccessful and death occurs.This underscores the critical importance of education,avoidance,and prevention(Table I-7). Therefore,patients should be educated regarding avoidance mea-sures for known or suspected triggers of anaphylaxis.This should take into consideration factors such as the patient’s age,concomi-tant conditions,activity,occupation,hobbies,residential condi-tions,access to medical care,and level of personal anxiety. Education should emphasize hidden allergens,cross-reactivity between various food or drug allergens,and unforeseen risks dur-ing medical procedures.
Patients discharged from emergency care of anaphylaxis should receive instruction on prevention of future episodes and when and how to administer AIE,with an understanding that these measures are not a substitute for emergency medical attention during anaphylaxis.Similar instruction of family,friends,and teachers or other caregivers(if applicable)could be optimal.After emergency treatment,the patient should be seen in consultation by an allergist or immunologist to review potential causes,prevention,and treatment of subsequent episodes.
Awareness of risk factors for anaphylaxis is important in pre-venting the occurrence of such reactions.Major risk factors for anaphylaxis include,but are not limited to,a history of such re-actions,patient exposure to the possible trigger(s),and atopic background.An atopic background could be a risk factor for sem-inal?uid anaphylaxis,exercise-induced and latex-induced anaphylaxis(and possibly IgE-independent reactions to RCM),but not anaphylactic reactions to medications.This is particularly important for patient avoidance of possible triggers.
Avoidance measures can be successful in any given patient if future exposure to known culprit allergens for that patient can be prevented.However,avoidance measures must be individualized, taking into consideration the patient’s age,activity,occupation, hobbies,residential conditions,access to medical care,and level of personal anxiety.
Parenteral administration of medication usually produces more severe reactions than oral administration.Therefore,drugs should be administered orally whenever possible.If parenteral adminis-tration is required,the patient should remain under medical observation for20to30minutes after the drug or other biologic agent is given.One might consider a waiting period of1to2hours if a patient receives an oral medication in the of?ce that the patient has never taken.Instances of anaphylaxis resulting from drug mislabeling are rare but do occur.Therefore,proper labeling of
episode,the contents of the container should be checked against the label.
Patients who will be exposed to known triggers of a prior re-action can in some cases be protected by(1)pharmacologic pro-phylaxis,(2)allergen(ie,venom)immunotherapy,or(3)short-term desensitization.Anti-IgE therapy alone or in combination with other therapeutic modalities might assist in the prevention of some forms of anaphylaxis,but further study is needed to de?ne that role.Oral immunotherapy or sublingual immunotherapy with food allergens(eg,peanuts,milk,or eggs)have been explored in scien-ti?cally rigorous trials,but these methodologies are not yet ready for use outside controlled trials approved by research ethics review boards.At times,pharmacologic prophylaxis can be used to prevent recurrent anaphylaxis.For example,regimens have been used successfully to prevent reactions to RCM and idiopathic anaphylaxis.
Special note should be given to the prevention of reactions to RCM in a patient who has had an anaphylactoid event to its administration and must receive a contrast reagent again.There is a question of whether skin testing is an effective means to select an agent that might be least likely to produce a repeat event.Although some studies have suggested that skin tests might be helpful in this regard,79the results of these investigations have not been con?rmed,80and at this time there does not appear to be enough evidence to suggest the use of skin testing for this purpose.
Many pretreatment protocols have been used to successfully prevent recurrent reactions to RCM.These include an H1antagonist alone,prednisone alone,prednisone plus an H1antagonist,pred-nisone plus an H1antagonist and ephedrine,the combination of an H1and an H2antagonist,prednisone plus an H1antagonist and an H2antagonist,and prednisone plus an H1antagonist and an H2 antagonist and ephedrine.81Perhaps the best studied of these is the one suggested in the present parameter,which consists of the use a lower osmolar preparation and premedication with50mg of prednisone by mouth13,7,and1hours before the procedure and 50mg of diphenhydramine intramuscularly1hour before the procedure.81This protocol was derived in studies involving only adult patients.There are no studies involving pediatric patients,but the American College of Radiology Manual on Contrast Media2013 update has suggested the following protocol:0.5to0.7mg/kg of prednisone orally13,7,and1hours before contrast injection and 1.25mg/kg of diphenhydramine orally(up to a maximum of50mg) 1hour before contrast injection.
They note that appropriate intravenous doses can be substituted in patients who cannot orally ingest medications(http:// https://www.doczj.com/doc/3c11467090.html,/wp-content/uploads/2014/03/170675431-2013-Contrast-Media-ACR-v-9.pdf?utm_source?download&utm_medium ?website&utm_campaign?2013-Contrast-Media-ACR).
Any patient who has experienced an episode of anaphylaxis is at increased risk for further events.Therefore,all patients who have had an episode should be managed as follows:
1.A prescription for an automatic epinephrine injector,4of which
are currently available(Table I-8),should be given to the patient, and the patient should be personally instructed in the use of the injector.It should be noted that the technique used to administer an automatic epinephrine injector can vary according to the type of injector.
2.Patients should wear identi?cation jewelry(eg,MedicAlert
Foundation,2323Colorado Avenue,Turlock,CA95382).
3.An anaphylaxis action plan should be given to the patient.
Various plans are available at the Web sites of the American Academy of Allergy,Asthma,and Immunology and the American College of Allergy,Asthma,and Immunology.
4.If there is any question about the diagnosis,the patient should
another episode does occur.The letter should request determi-nation of a serum tryptase level and possibly24-hour urinary histamine and prostaglandin D2levels.
5.If the etiology of the original anaphylactic event was a drug,then
the patient should be educated regarding drugs that might cross-react with the original culprit(eg,penicillin and other b-lactam antibiotics).
6.Consideration should be given to the discontinuation of any drug
that might worsen an episode or complicate its treatment.Drugs with the potential of doing so include b-adrenergic blockers,ACE inhibitors,a-adrenergic blockers,some tricyclic antidepressants (eg,amitriptyline),and possibly monoamine oxidase inhibitors, angiotensin receptor blockers,and renin inhibitors.6,17e19Other risk factors that can increase the frequency or severity of a re-action or complicate the treatment also should be considered and modi?ed when possible.These factors include age,asthma, comorbidities,use of alcohol,and presence of mastocytosis (Table I-9).
7.In any patient who has experienced an anaphylactic event,one
should consider a referral to an allergist or immunologist.It has been demonstrated that such a referral can improve outcomes by further re?ning the diagnosis and establishing the cause of the event.
78
Table I-1
Signs and symptoms of anaphylaxis a
Data were derived from the following references:Lieberman P,Nicklas R,Oppen-heimer J,et al.The diagnosis and management of anaphylaxis practice parameter: 2010update.J Allergy Clin Immunol.2010;126:477e480;Wood R,Camargo CA, Lieberman P,et al.Anaphylaxis in America:results from a national physician survey. Ann Allergy Asthma Immunol.2012;109(suppl):A20;and Boyle J,Camargo CA,Lie-berman P,et al.Anaphylaxis in America:results from a national telephone survey.J Allergy Clin Immunol.2012;129(suppl):AB132.
b Percentages are
approximations.
Table I-2
Essential features of history in the evaluation of a patient who has experienced an episode of anaphylaxis
Table I-3
Differential diagnoses:entities,in addition to anaphylaxis,and causative agents to be considered when a patient presents to your of ?ce with symptoms suggestive of an anaphylactic episode including anaphylaxis
Table I-4
Tests useful in establishing a diagnosis of anaphylaxis,a condition mimicking anaphylaxis,or establishing the causal event
Table I-5
World Health Organization criteria for systemic mastocytosis a
From Swerdlow SH,Campo E,Harris NL,et al.Mastocytosis (mast cell disease).In:World Health Organization (WHO)Classi ?cation of Tumours .Vol 2.Lyon,France:IARC Press;2008:54e
63.
Table I-6
Suggested criteria for the diagnosis of mast cell activating syndrome
Table I-7
Prevention of further episodes
Table I-8
Available automatic epinephrine injectors in the United States All these devices are available in doses of 0.15and 0.3mg.
Annotation 1:Is the history consistent with a previous episode of anaphylaxis?
All individuals who have had a known or suspected anaphylactic episode require a careful and complete review of their clinical history.This history can elicit manifestations such as urticaria,angioedema,?ushing,pruritus,upper airway obstruction,gastro-intestinal symptoms,syncope,hypotension,lower airway obstruction,and/or other less common manifestations.
Of primary importance is the nature of the symptoms charac-terizing the event.Essential questions to be asked are:
1.Were there cutaneous manifestations (speci ?cally pruritus,?ushing,urticaria,or angioedema)?
2.Was there any sign of airway obstruction involving the upper or lower airway?
3.Were there gastrointestinal symptoms (ie,nausea,vomiting,or diarrhea)?
4.Were syncope or presyncopal symptoms present?
The absence of cutaneous symptoms puts the diagnosis in question because most anaphylactic episodes include cutaneous symptoms (Table I-2),although their absence does not rule out anaphylaxis.The history should concentrate on agents encountered before the reaction.Whenever appropriate,the information should be obtained from not only the patient but also from family mem-bers or other witnesses of the event.The complete sequence of events must be reviewed,with special attention paid to cardiore-spiratory symptoms.Medical records,including medication re-cords,often can be useful in evaluating the history,physical ?ndings,and treatment of the clinical event.In addition,the results of any previous laboratory studies (eg,serum tryptase)could be helpful in making the diagnosis of anaphylaxis or distinguishing it from other entities.
Annotation 1A:Consider consultation with allergist or immunologist
Evaluation,diagnosis,and long-term management can be complex.The allergist or immunologist has the training and expertise to obtain a detailed allergy history;coordinate laboratory and allergy testing;evaluate the bene ?ts and risks of therapeutic options;and counsel the patient on avoidance measures.For these reasons,patients with a history of anaphylaxis should be consid-Annotation 2:Pursue other diagnoses or make appropriate referral Other conditions that should be considered in the differential diagnosis include (1)vasodepressor (vasovagal or neurocardiogenic)syncope,(2)syndromes that can be associated with ?ushing (eg,metastatic carcinoid),(3)postprandial syndromes (eg,scombroid poisoning),(4)SM,(5)psychiatric disorders that can mimic anaphy-laxis such as panic attacks or vocal cord dysfunction syndrome,(6)angioedema (eg,hereditary angioedema),(7)other causes of shock (eg,cardiogenic),and (8)other cardiovascular or respiratory events.Annotation 3:Is cause readily identi ?ed by history?
The history is the most important tool to establish the cause of
Table I-9
Factors that can increase the risk for an anaphylactic event,increase its severity,or complicate its treatment a Data were derived from references 16through 19and 79through
90.
Figure I-1.Algorithm for initial evaluation and management of a patient with a previous episode of anaphylaxis.
history of all food consumed and drugs taken during the4to6hours before the episode should be obtained.In addition,the labels for all packaged foods ingested by the patient in this period of time should be reviewed because a substance added to the food could be responsible.A history of any preceding bite or sting should be ob-tained.The patient’s activities(eg,exercise,sexual activity)pre-ceding the event should be reviewed.Patient diaries could be a useful adjunct in con?rming or identifying the cause of anaphylaxis. Annotation4:Consider idiopathic anaphylaxis
Idiopathic anaphylaxis is a diagnosis of exclusion that should be made only after other causes of anaphylaxis and other differential diagnoses have been considered.
Annotation5:Are further diagnostic tests indicated:allergy skin tests,in vitro tests,or challenge tests?
Skin tests and/or in vitro tests for speci?c IgE and challenge tests might be appropriate to help de?ne the cause of the anaphylaxis. However,the history could be so conclusive that none of these tests are necessary.
Annotation6:Diagnosis established based on history;risk of testing; limitation of tests;patient refuses test;other management options available;management
There might be circumstances in which skin tests or in vitro speci?c IgE and/or challenge tests might not be warranted.In general,this could apply when the clinician decides to proceed with management because the history is conclusive.The history of anaphylaxis to a speci?c agent might be so strong that testing is unnecessary and inappropriate from the risk-vs-bene?t standpoint. If avoidance can be easily and safely accomplished,testing might not be necessary.
Testing or challenge with reagents to a suspected allergen might not be available or the predictive value of the test might be in question.Challenge tests(and,to a lesser extent,skin tests)can be hazardous and not acceptable from a risk-vs-bene?t standpoint,if other management options are available.Occasionally patients might refuse to have the test.
Annotation7:Testing identi?es speci?c cause of anaphylaxis Skin tests or in vitro tests can determine the presence of speci?c IgE antibodies to foods,medications(eg,penicillin and insulin),and stinging insects as a cause of anaphylaxis.For most medications, standardized in vivo and/or in vitro testing is not available.
In general,skin testing is more sensitive than in vitro testing and is the diagnostic procedure of choice for evaluation of most po-tential causes of anaphylaxis(eg,penicillin and insect stings). However,it is essential that the correct technique for skin testing be used.When possible,standardized extracts for skin testing should be used,although occasionally fresh-food extracts will be superior to available standardized extracts.If the skin testing extract has not been standardized(eg,latex,protamine,or antibiotics other than penicillin),the clinical relevance of the results might be uncertain. If skin testing is performed,then it should be done under the su-pervision of a physician who is experienced in the procedure in a setting with appropriate rescue equipment and medication.
The accuracy of in vitro testing depends on the reliability of the in vitro method,the ability to interpret the results,and the avail-ability of reliable testing material.The clinical signi?cance of skin testing or in vitro test depends on the ability to correlate the results of such testing with the patient’s history.
If tests for speci?c IgE antibodies(ie,skin tests and/or in vitro tests)do not provide conclusive evidence of the cause of anaphy-laxis,challenge with the suspected agent can be considered.Chal-lenge procedures also might be appropriate in patients who other NSAIDs).Challenge with suspected agents must be done carefully by individuals knowledgeable in the challenge procedure and with expertise in managing reactions to the challenge agent if they should occur.
Annotation8:Reconsider clinical diagnosis;reconsider idiopathic anaphylaxis;consider other triggers;consider further testing; management
At this stage in the patient’s evaluation,it is particularly important to consider other possible causes of anaphylaxis or a different diagnosis.The history and test results should be reviewed. Further testing for speci?c IgE antibodies should be considered. Laboratory studies that might be helpful include serum tryptase, urinary5-hydroxyindoleacetic acid,urinary methylhistamine, chromogranin A,vasointestinal polypeptide,and catecholamines. Idiopathic anaphylaxis is a diagnosis of exclusion(see section on idiopathic anaphylaxis).Management of anaphylaxis should follow annotation10(see below).
Annotation9:Diagnosis made of speci?c cause of anaphylaxis The diagnosis of a speci?c cause of anaphylaxis can be sup-ported by the results of skin tests,in vitro IgE tests,and/or challenge tests(particularly double-blinded,placebo-controlled challenge tests).
Annotation10:Management of anaphylaxis
When anaphylaxis has occurred because of exposure to a spe-ci?c agent(eg,food,medication,or insect sting),patients should be educated about agents or exposures that would place them at risk for future reactions and be counseled on avoidance measures that can be used to lower the risk for such exposures.Patients who have had anaphylactic reactions to food should be instructed on how to read food ingredient labels to identify foods that they should avoid. Patients with anaphylaxis to medications should be informed about all cross-reacting medications that should be avoided.Should there be a future essential indication for use of incriminated medications, it might be helpful to educate patients about applicable manage-ment options(eg,medication pretreatment and use of low osmo-larity agents in patients with a history of reactions to RCM or desensitization for drugs such as antibiotics).Patients who have had an anaphylactic reaction to an insect sting should be advised about avoidance measures to decrease the risk of an insect sting and usually are candidates for insect VIT.Patients who have had anaphylaxis should carry self-injectable epinephrine if there is continued risk for anaphylaxis.Patients also should carry identi?-cation indicating that they have experienced anaphylaxis and indicating the responsible agent.
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II.Of?ce Management of Anaphylaxis
Summary Statement9:Plan for appropriate of?ce response to anaphylaxis by(1)educating staff and patients,(2)preparing an anaphylaxis emergency cart,and(3)developing an of?ce action plan for anaphylaxis management to maintain pro?ciency in anaphylaxis management.[Strong Recommendation;D Evidence] Summary Statement10:Prepare all of?ce staff(clerical,nursing, and primary providers)to recognize and monitor the patient for the early signs and symptoms of anaphylaxis in preparation for epinephrine administration.[Strong Recommendation;D Evidence] Summary Statement11:At the onset of anaphylaxis,(1) administer epinephrine intramuscularly in the mid-outer thigh;(2) remove the inciting allergen,if possible(eg,stop an infusion);(3) quickly assess airway,breathing,circulation,and mentation and summon appropriate assistance from staff members;and(4)start, if needed,cardiopulmonary resuscitation and summon EMS. [Strong Recommendation;D Evidence]
Summary Statement12:After administering epinephrine,notify EMS for patients having severe anaphylaxis and/or patients not responding to epinephrine.[Strong Recommendation;C Evidence] Summary Statement13:Place and maintain patients in a supine position,unless the respiratory compromise contraindicates it,to prevent or to counteract potential circulatory collapse.Place preg-nant patients on their left side.For maintaining hemodynamic stability,intravenous access is essential.[Recommendation;C Evidence]
Summary Statement14:Administer oxygen to select patients in anaphylaxis.[Strong Recommendation;C Evidence]
Summary Statement15:Make a rapid and ongoing assessment of the patient’s airway status and maintain airway patency using the least invasive but effective method(eg,bag-valve-mask). [Strong Recommendation;D Evidence]
Summary Statement16:Initiate intravenous?uid replacement patients who do not respond to intramuscular epinephrine.[Strong Recommendation;C Evidence]
Summary Statement17:In addition to epinephrine adminis-tered for anaphylaxis,consider administering a nebulized b2-agonist(eg,albuterol)for signs and symptoms of bronchospasm. [Recommendation;B Evidence]
Summary Statement18:In patients receiving b-adrenergic blocking agents,administer glucagon if they have not responded to epinephrine.[Strong Recommendation;C Evidence]
Summary Statement19:Never administer H1and H2antihis-tamines or corticosteroids as initial therapy for anaphylaxis instead of epinephrine and consider these agents optional or adjunctive therapy.[Strong Recommendation;B Evidence]
Summary Statement20:Individualize the duration of direct observation and monitoring after anaphylaxis but provide longer periods of observation for those patients with a history of risk factors for severe anaphylaxis(eg,asthma,previous biphasic re-actions,or protracted anaphylaxis)for at least4to8hours.[Strong Recommendation;C Evidence]
Summary Statement21:Prescribe AIE for patients who have experienced an anaphylactic reaction and for those at increased risk for anaphylaxis.[Strong Recommendation;C Evidence] Summary Statement22:Provide patients at risk for anaphylaxis with an action plan instructing them on how to manage an episode of anaphylaxis,including administration of epinephrine[Recom-mendation;C Evidence]
Education on the triggers and early signs and symptoms of anaphylaxis must be a structured,reoccurring,and scheduled process for all of?ce staff,medical and clerical,and patients (Table II-1).The patient’s education on anaphylaxis should start at the time of the new patient visit for all patients who present with signs and symptoms of anaphylaxis and for all patients who will be undergoing a diagnostic or treatment procedure that could result in anaphylaxis(eg,allergy skin testing).The educational process will involve obtaining consent,preferably written,for any invasive procedure(eg,SCIT)and will continue throughout the course of treatment.Staff and patients must recognize that any signi?cant change in clinical status or the onset or increase of symptoms, however subtle,that occurs immediately after in-of?ce AIT or diagnostic or therapeutic procedures,or possible ingestion of a known food or medication allergen should be considered anaphy-laxis.1Anaphylaxis must be viewed as“a serious allergic reaction that is rapid in onset and may cause death”for which the only treatment is epinephrine.2
Appropriate management of anaphylaxis requires all of?ces that administer parental medications,including AIT,antibiotics, vaccines,and g-globulin.These should be organized in such a way that they are readily accessible and can be easily moved to the patient experiencing anaphylaxis.Based largely on expert opinion, Table II-2presents a list of the key anaphylaxis supplies and equipment that are considered(1)?rst line(required supplies and priority medications),(2)second line,and(3)third line(recom-mended for special settings).First-line items are a stethoscope,a sphygmomanometer,injectable epinephrine1:1,000,oxygen, intravenous0.9normal(NL)saline,a1-way valve facemask, oropharyngeal and nasal pharyngeal airways,disposable face masks,oxygen saturation monitor,albuterol inhalational solution (0.05%),glucagon,and the necessary supplies to administer these items.A written emergency protocol and?ow chart for directing and recording times and events during treatment also should be considered?rst-line items.3e7Second-line supplies and medications include a mixture of what can be considered“optional”items(eg, antihistamines and corticosteroids)and advanced airway and car-diovascular support items(eg,laryngeal mask airways and an auto-mated external de?brillator)that should be considered for maximum
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appropriate in areas in which EMS might be delayed by more than10 minutes.The anaphylaxis cart must be inventoried on a regular basis (eg,every3months)and kept up to date by using the detailed listing of medications,supplies,and equipment as a checklist.
All allergists in their individual practice settings should collab-orate with their nursing staff to develop a customized written protocol for the management of anaphylaxis in the of?ce.Several action plans for anaphylaxis management in the of?ce setting have been published.4,6e8A revised of?ce-based anaphylaxis treatment protocol is presented in Table II-3.The anaphylaxis action plan should follow evidence-based guidelines and should provide a detailed stepwise approach based on symptoms and the patient’s response to treatment.It can take the form of an algorithm,a table, a graph,or even a combination of these,but it must be easy to read and follow during an emergency.Ideally,it would include assigned roles for each staff member,by position or name,to be followed during anaphylaxis management.Once developed,it should be posted in all patient care areas of the of?ce and with the emergency supplies for ready access.8
The importance of mock drills to deal with emergency situations is well recognized and used by hospitals(required annually by the Hospital Joint Commission under the jurisdiction of the Agency for Healthcare Research and Quality),public schools(eg,?re drills), airline pilots(eg,?ight simulators),and emergency medical personnel(eg,disaster response drills),to name a few.Likewise,the successful management of anaphylaxis requires that of?ce staff must immediately activate the response team and expeditiously deliver appropriate treatment.6This can be accomplished only with frequent(eg,periodic),organized,mock anaphylaxis drills in which all staff members,clerical and medical,are required to participate.6,8 Maintaining clinical pro?ciency with anaphylaxis management involves certi?cation in basic cardiopulmonary resuscitation and, ideally,advanced life support to insure the proper skillset for treatment of refractory anaphylaxis,including airway management, cardiac compressions,venous and intraosseous access,and parental medication calculation and delivery.6,9
The initial assessment and treatment of the patient in anaphy-laxis involves several critical steps that should be started con-comitantly4,6,10e12(Table II-3).Urgent treatment is based on the ?nding that there is often a very short time(eg,5minutes for an iatrogenic intravenously administered allergen such as an antibiotic and30minutes for food-induced anaphylaxis)from the onset of mild symptoms to respiratory or cardiac arrest.1
Although removal of the inciting allergen is ideal,this will rarely apply in the of?ce setting because parental or ingestion will usually have been completed before the onset of symptoms.However,with medication infusions or oral challenges with food or medications, the procedure should be stopped as soon as signs and symptoms of even mild anaphylaxis are noted.4,13
The?rst member of the of?ce staff to recognize that the patient is experiencing anaphylaxis must be prepared to evaluate the airway,breathing,circulation,and mentation.If the patient has moderate to severe anaphylaxis or is showing signs and symptoms of impending cardiopulmonary arrest,EMS must be summoned immediately in addition to all available of?ce medical staff.Car-diopulmonary resuscitation should be started immediately in the event of cardiopulmonary arrest,with emphasis on adequate chest compressions without interruption(Table II-4).Ventilations can be given once there are2medical staff members at the patient’s side. For imminent or established cardiopulmonary arrest,rapidly establish venous access and administer an intravenous bolus dose of epinephrine because ventricular arrhythmias have been reported after epinephrine administration.For adults,the dose is1mg intravenously(as a1:10,000dilution).For a child,the dose is0.01 mL/kg to a maximum single dose of1mg(give as a1:10,000cardiopulmonary resuscitation is continued.4,15,16The same dose can be administered through the intraosseous route if an intrave-nous line cannot be established.15If the intravenous or intraosseous route is not available,epinephrine can be given by endotracheal administration if the advanced airway is in place.(Adult dose is 2e2.5mg of1:1,000diluted in5e10mL of sterile water.Pediatric dose is0.1mg/kg to a maximum of2.5mg given as a1:1,000so-lution diluted in5e10mL of sterile water.17)
The treatment of anaphylaxis is,at best,based on indirect and observational studies and primarily on consensus.Observational studies and analysis of near-fatal and fatal reactions have shown that prompt and decisive treatment of any SR,even a mild one,with epinephrine prevents progression to more severe symptoms.6,18 The most common trigger for anaphylaxis in the allergy of?ce setting is the administration of SCIT.Having the patient under direct observation for30minutes offers the unique opportunity to observe for the early signs and symptoms of anaphylaxis.Rapid administration of a single dose of epinephrine for mild symptoms of anaphylaxis resulting from AIT almost always stops the pro-gression of symptoms,with no additional epinephrine injections being required.19
In contrast,delayed administration of epinephrine is often believed to be the major contributing factor to fatalities.1,20e26In food-induced fatal to near-fatal anaphylaxis,it has been reported that of7of13children who survived,6had received epinephrine within the30minutes of ingesting the allergen.Of the6fatalities, only2children had received epinephrine within60minutes.20 Anaphylaxis guidelines are in agreement that epinephrine should be administered intramuscularly into the lateral thigh.2,4,12,27e29Published studies on epinephrine pharmacoki-netics in patients not in anaphylaxis have shown that intramuscular administration in the vastus lateralis muscle produces a more rapid rate of increase in blood epinephrine levels than subcutaneous or intramuscular administration in the deltoid muscle.Unfortunately, there are no studies evaluating the pharmacokinetics of a subcu-taneous injection in the lateral thigh.Moreover,it is not clear what the pharmacokinetics would be in patients in anaphylaxis and/or what the most desirable pro?le would be in that setting.Likewise, outcome measurements of therapeutic effectiveness of intramus-cular vs subcutaneous injection are lacking and these might never be available owing to ethical concerns.
The adult dose of1:1,000epinephrine is0.2to0.5mL,whereas the pediatric dose is0.01mg/kg,with a maximum of0.3 mg.4,6,15,30,31A higher dose(eg,0.5mL)within the recommended dose range should be considered in patients with severe anaphy-laxis.If there has not been signi?cant improvement in symptoms, then the dose can be repeated approximately every5to15minutes, as the physician deems to be necessary,usually moving to intra-venous administration of epinephrine in conjunction with getting the patient to a medical setting where continuous monitoring can be done if there has been no response after3to4intramuscular injections.It has been shown that a repeat dose is required up to 35%of the time.4,6,32,33
Monitor and record the patient’s blood pressure,cardiac rate and function,respiratory status,and oxygenation at frequent and regular intervals.Start frequent oxygen saturation measurement, start continuous noninvasive monitoring,and obtain an electro-cardiogram,if available.4
There is universal agreement that most patients should be placed in a supine position during anaphylaxis.4,6However,whether to elevate the legs is controversial.Although some guidelines continue to recommend the Trendelenburg position(feet are elevated 15e30 higher than the head)for the management of shock,the American Heart Association and the American Red Cross in a2010 consensus document concluded that there is insuf?cient evidence to
shock.34In the Prehospital Trauma Life Support Manual,the American National Association of Emergency Medical Technicians and the American College of Surgeons recommend using the supine position but explicitly discourage the Trendelenburg position or its variants for the management of shock.35
The proposed physiologic rationale for the Trendelenburg po-sition is that it will shift intravascular volume from the lower ex-tremities and abdomen to the upper part of the thorax,the heart, and the brain,thus improving perfusion to heart and brain.How-ever,the evidence to support this rationale is very limited and often con?icting.In the normotensive patient and even the elderly pa-tient who might have impairment of vasomotor control,placement in the Trendelenburg position does not demonstrate any delete-rious hemodynamic effect and theoretically might help prevent hypotension.36e39
In contrast,patients with hypotension show no improvement in blood pressure,cardiac index,or tissue oxygenation with the use of the Trendelenburg position.36,39e47Potential complications of the Trendelenburg position for the normotensive and hypotensive pa-tient include decreased lung compliance,vital capacity,and tidal volume;increase in arterial partial pressure of carbon dioxide; decreased arterial partial pressure of oxygen;and increase in the work of breathing.39,44,46e49
If the patient is having respiratory dif?culty,consider having the patient sit up.There also is a possible increase in intracranial pressure associated with an increase in central venous pres-sure.36,50e53A recent systematic review of all articles on the effect of Trendelenburg position on hemodynamic status published before March2011concluded that the evidence was too inconsis-tent to support that the Trendelenburg position or even passive leg lifting as bene?cial in hemodynamically compromised patients.54 Given this con?icting evidence,it would seem prudent to place the patient in the supine position but without leg elevation.
In a retrospective study of10anaphylactic fatalities,there appeared to be an association with fatality when there was a change in position from a supine to an upright or standing position during anaphylaxis.Although the investigators recommended maintaining a supine position during anaphylaxis,they did not recommend the Trendelenburg position.55
Administration of oxygen is the second most important thera-peutic intervention,second only to epinephrine administration,for the treatment of anaphylaxis and should be considered for all pa-tients experiencing anaphylaxis regardless of their respiratory status.6It is imperative to administer oxygen for any patient with respiratory or cardiovascular compromise and to patients who do not respond to the initial treatment with epinephrine.Oxygen up to 100%should be administered at a?ow rate of6to10L/min through a facemask.Ideally,oxygen saturation should be monitored and kept at94%to96%by oximetry.4,13,56
In most of?ce settings,bag-valve-mask ventilation will be the method of choice to support ventilation in the event of respiratory failure or arrest.It is most effective when2individuals can support the airway.One person opens the airway with the head-tilt and chin-lift maneuver and seals the mask to the face,covering the nose and mouth.The second person squeezes the bag and the2rescuers look for adequate chest rise.It is recommended that approximately 600mL of tidal volume for1second using an adult(1e2L)bag be delivered.Supplementary oxygen at a?ow rate of10to12L/min should be used.Two breaths are delivered during a3-to4-second pause after every30chest compressions.57An oropharyngeal airway can aid in the delivery of adequate ventilation in an un-conscious patient with no cough or gag re?ex.Improper insertion can result in displacement of the tongue into the hypopharynx, resulting in airway obstruction.The nasopharyngeal airway might be better tolerated by patients who are not deeply unconscious and airway bleeding in up to30%of patients.57,58The training,skill,and experience of the physician should guide the selection of the most appropriate airway for the patient.When the provider can adequately ventilate the patient using the bag-valve-mask,there is no evidence that the use of advanced airway measures improves survival rates of out-of-hospital cardiac arrest.57
It is recommended that all Advanced Cardiovascular Life Sup-port providers be trained and experienced in the insertion of1 advanced airway because there will be times when the bag-mask is inadequate.57Advanced upper airway management can use the endotracheal tube or a supraglottic airway.The incidence of com-plications is unacceptably high when endotracheal intubation is performed by an inexperienced provider or monitoring of the tube is inadequate.57Use of a supraglottic airway(eg,laryngeal mask airway),esophageal-tracheal tube(Combitube),or laryngeal tube (King LT)is believed to be a reasonable alternative to the endo-tracheal intubation and its use can be accomplished without interruption of chest compressions.57In fact,for those trained in their use,these supraglottic airway devices are no more compli-cated to use than the bag-value-mask device because direct laryngoscopy of the airway is not required.57The supraglottic airway also offers some protection against aspiration.Some studies have shown that the laryngeal mask airway provides equivalent ventilation compared with the endotracheal tube.59,60There are no randomized clinical trials that have compared bag-valve-mask with endotracheal intubation in adult patients with cardiac arrest,but1 such study in children showed no survival advantage for endotra-cheal intubation in the out-of-hospital arrest.61
In the hands of a very experienced provider,endotracheal intubation offers protection against aspiration and gastric insuf-?ation,is the most effective method for ventilation and oxygena-tion,facilitates the use of suctioning,and allows for the delivery of drugs through the endotracheal tube.However,upper airway obstruction(eg,severe laryngeal edema)is an absolute contrain-dication for endotracheal intubation and should never be consid-ered a substitute for a surgical airway in this setting.It has been suggested that inhaled epinephrine or intratracheally administered epinephrine might decrease oropharyngeal edema,making airway management less dif?cult.
The use of cricothyrotomy should be reserved for life-and-death situations when obstruction(eg,angioedema)above the larynx prevents adequate ventilation,even with the endotracheal tube. The use of the needle cricothyroidotomy,as a temporary airway, can be used for children and adults and is most likely the easiest for the inexperienced provider to use.62The procedures should take approximately2minutes to perform and makes use of a14-gauge needle,syringe,canula,and Y-connector.If expiration is not possible through the cannula,then one should decrease the oxygen ?ow and limit use to shorter than45minutes because carbon di-oxide retention will become signi?cant.63A purpose-built kit(eg, Mini-Trach II)also could be considered but requires experience to use.64
Hypotension should be treated with rapid?uid replacement using1to2L of0.9%normal saline,infused rapidly(eg,5e10mL/kg within the?rst5minutes for an adult and up to30mL/kg in the ?rst hour for children).6Large-bore(14-to16-gauge for adults) intravenous catheters should be used.13For the normotensive pa-tient in anaphylaxis,starting NL saline at an appropriate mainte-nance rate for weight(eg,125mL/h for adults)to maintain venous access for medications and/or rapid?uid replacement is often unnecessary.13
Intravenous administration of epinephrine will rarely be necessary in the of?ce setting and should be administered in a monitored setting with a programmable infusion pump to titrate appropriately.65However,if there is no response to multiple in-
中国急性缺血性脑卒中诊治指南 急性期诊断与治疗 一、评估和诊断 (一)病史和体征 1．病史采集：询问症状出现的时问最为重要。 2．一般体格榆查与神经系统体榆：评估气道、呼吸和循环功能后，立即进行一般体格检查和神经系统体检。 3．可用脑卒中量表评估病情严重程度。常用量表有： (1)中国脑卒中患者临床神经功能缺损程度评分量表。 (2)美国国立卫生院脑卒中量表(National Institutes of}tcalth Strok|(NIHss)是目前国际上最常用量表。 (3)斯堪的纳维亚脑卒中量表(ScandinavianStmke Seale，SSS)。 (二)脑病变与血管病变检查 脑部病变检查：1 平扫CT，疑似脑卒中首选检查；2 多模式CT；3 标准MRI；4多模式MRI。 血管检查：1 颈动脉双功超声；2 TCD；3 MRA、CTA、DSA （三）实验室及影像检查选择 所有患者都应做的检查：①平扫脑cT或MRl；②血糖、肝肾功能和电解质；③心电图和心肌缺血标志物；④全血计数，包括血小板计数；⑤凝血酶原时问(Frr)、国际标准化比率(INR)和活化部分凝血活酶时问(AHT)；⑥氧饱和度；⑦胸部x线检查。 部分患者必要时可选择的检查：①毒理学筛查；②血液酒精水平；③妊娠试验；④动脉血气分析(若怀疑缺氧)；⑤腰穿(怀疑蛛网膜下腔出血而cT末显示或怀疑脑卒中继发于感染性疾病)；⑥脑电图(怀疑癫痫发作)。 （四）急性缺血性脑卒中的诊断可根据： (1)急性起病； (2)局灶件神经功能缺损，少数为全面神经功能缺损； (3)症状和体征持续24 h以上（溶栓可参照适应证选择患者）； (4)排除非血管性脑部病变； (5)脑CT或MRI排除脑出血和其他病变，有责任缺血病灶。 （五）急性缺血性脑卒中诊断流程应包括如下5个步骤 (1)是否为脑卒中，排除非血管性疾病。 (2)是否为缺血性脑卒中，进行脑CT或MRI检查排除出血性脑卒中。 (3)脑卒中严重程度，根据神经功能缺损量表评估。 (4)能否进行溶栓治疗，核对适应证和禁忌证（见溶栓中相关内容）。 (5)病因分型参考TOAST标准，结合病史、实验窜、脑病变和血管病变等检查资料确定病因。 推荐意见：(1)对所有疑似脑卒中患者应进行头颅平扫CT或MRI检查（I 级推荐）。(2)在溶栓等治疗前，应进行头颅平扫CT检查（I级推荐）。(3)应进行上述血液学、凝血功能和生化检查（I级推荐）。(4)所有脑卒中患者应进行心电图检查（I级推荐）。(5)用神经功能缺损量表评估病情程度（Ⅱ级推荐）。(6)应进行血管病变检查（Ⅱ级推荐），但在症状出现6 h内，不过分强调此类检查。(7)根据上述规范的诊断流程进行诊断（I级推荐）。
2017～2018年国内外高血压指南合集(附全文下载)
2017～2018年国内外高血压指南合集（附全文下载） 5月17日是“世界高血压日”。高血压的诊疗是目前的研究热点之一，也是存在争议比较多的一个领域。2017～2018年期间国内外发布了很多部高血压指南，医脉通汇总如下，供大家参考。 中国指南 1中国急诊高血压诊疗专家共识 急诊高血压包括高血压急症和高血压亚急症。在高血压患者中有1%～2%会发生高血压急症。2018年1月发布的《中国急诊高血压诊疗专家共识（2017版）》指出，急诊高血压治疗的原则是迅速评估患者病情，区分高血压急症和高血压亚急症，根据病情评估进行针对性治疗。 文章链接：急诊高血压：遇到这13种情况，该怎么处理？下载地址：https://www.doczj.com/doc/3c11467090.html,/guideline/14854 2我国高血压诊断标准及降压目标声明 2017年11月，美国发布高血压新指南，将高血压定义修改为血压≥130/80 mmHg，一时间引起了广泛的关注和较大的争议。同年12月，中国医师协会组织专家召开了研讨会，对美国高血压新指南有关高血压诊断及降压标准等方面问题进行了讨论，最终达成共识，形成了《中国医师协会关于我国高血压诊断标准及降压目标科学声明》。
文章链接：中国新版高血压指南还没来，科学声明先来啦！下载地址：https://www.doczj.com/doc/3c11467090.html,/guideline/15534 3老年高血压诊治中国专家共识2017 与中青年患者相比，相似程度的血压升高，老年人发生心脑血管事件的危险显著升高。老年高血压的诊治存在特殊性。《老年高血压的诊断与治疗中国专家共识（2017版）》中强调，老年人高血压的发病机制、临床表现等具有特殊性，应重视群体特征和治疗措施的个体化。文章链接：中国老年高血压共识2017最新发布！别再跟着美国跑啦~ 下载地址：https://www.doczj.com/doc/3c11467090.html,/guideline/14460 4国家基层高血压防治管理指南2017 基层医疗卫生机构是高血压管理的“主战场”。《国家基层高血压防治管理指南2017》主要内容包括基层高血压管理的基本要求、管理流程、诊断和评估、治疗方案及长期管理要求等。本指南可操作性强，适用于基层医疗卫生机构的医务工作者。 文章链接：国家基层高血压防治管理指南2017发布！ 下载地址：https://www.doczj.com/doc/3c11467090.html,/guideline/13888 5高血压合理用药指南（第2版） 在第1版《高血压合理用药指南》颁布2年之后，顺应高血压治疗形势的改变，国家卫生计生委合理用药专家委员会和中国医师协会高血压专业委员会组织进行该指南的更新和
中国血管性痴呆诊治指南解读 医脉通2013-08-22分享 《中国痴呆诊疗指南》是我国第一部痴呆的中西医结合循证指南。在北京大学卒中论坛第23次学术会议上，指南的主要制定者之一、北京中医药大学东直门医院副院长田金洲教授对其中的血管性痴呆诊治部分做了解读。 痴呆流行现状 近年来，我国痴呆患病率明显增高。传统认为，血管性痴呆（VaD）是仅次于阿尔茨海默病（AD）的第二位常见的痴呆原因。但目前数据显示，单纯血管性痴呆占仅所有痴呆的3%-5%，而混合性痴呆占比例较高。 我国目前大约有73.8%-93%的痴呆患者未被诊断。服药治疗的痴呆患者仅占所有患者的21.3%，服用一线抗痴呆药物的仅2%，多数痴呆患者没有接受规范治疗。 血管性痴呆的认识误区 目前在VaD认识上，存在以下几个误区：（1）认为血管性痴呆患病率高于阿尔茨海默病；（2）认为有卒中和痴呆就可以诊断为血管性痴呆；（3）认为在筛查痴呆时MoCA （蒙特利尔认知评估）的敏感性优于MMSE（简易精神状态检查）；（4）把血管病的基础治疗当成血管性痴呆的治疗。 此外，欧美指南很少引用中国的文献，其诊断和治疗的推荐意见并不适合中国的语言和文化背景。基于上述原因，我们制定了中国的痴呆诊治指南。 血管性痴呆的诊断 VaD的诊断标准有ICD-10、NINDS-AIREN和DSM-Ⅳ等，其中1993年Román等制定的NINDS-AIREN血管性痴呆诊断标准使用最广泛。它强调3个基本要素：（1）符合痴呆诊断，推荐ICD-10、DSM-Ⅳ和DSM-Ⅳ-TR诊断标准；（2）要有脑血管病的证据，推荐CT或MRI影像学检查证据；（3）两者必须有相关性，至少有以下中的一项：①在明确的卒中后3个月内发生痴呆，②突然认识功能衰退，或波动性、阶梯样进行性认知功能损害。 2000年DSM-Ⅳ-TR痴呆诊断标准：（1）发生多个认知领域功能障碍，包括以下两个方面：①记忆功能障碍；②至少同时具有以下认知功能损害之一：失语、失用、失认和执行功能障碍；（2）上述认知功能障碍必须严重到足以干扰社会或职业功能，而且与以往相比明显下降；（3）认知功能障碍不只是发生在谵妄过程中。 血管病证据强调：（1）梗死部位非常重要；（2）重视对血管病严重程度的判断。 血管性痴呆包括6个亚型：（1）多发性梗死性痴呆（MID），占75% ；（2）重要部位的单个梗死痴呆，例如丘脑梗死；（3）小血管病性痴呆，包括微梗死性痴呆、皮质下动脉硬化性脑病、脑白质病变、脑淀粉样血管病（可伴出血）；（4）低灌注性痴呆；（5）出血性痴呆，如丘脑出血；（6）其他，如CADASIL（常染色体显性遗传病合并皮质下梗死和白质脑病）。
临床诊疗指南及药物临床应用指南 1、社区获得性肺炎的诊断及治疗 2、扁桃体炎治疗指南 3、成人水痘的症状和治疗 4、急性阑尾炎诊疗规范 5、流行性腮腺炎诊断标准 6、带状疱疹治疗指南 7、丹毒诊治指南 8、皮肤感染指南 9、上消化道出血 10、抗菌药物的合理应用 11、激素的使用
社区获得性肺炎诊断和治疗指南 中华医学会呼吸病学分会 社区获得性肺炎(community-acquired pneumonia,CAP)是指在医院外罹患的感染 性肺实质(含肺泡壁，即广义上的肺间质)炎症，包括具有明确潜伏期的病原体感染而在入院后潜伏期内发病的肺炎。CAP是威胁人类健康的常见感染性疾病之一，其致病原的组成和耐药特性在不同国家、不同地区之间存在着明显差异，而且随着时间的推移而不断变迁。近年来，由于社会人口的老龄化、免疫损害宿主增加、病原体变迁和抗生素耐药率上升等原因，CAP的诊治面临许多新问题。最近，中华医学会呼吸病学分会完成了两项较大样本的全国性CAP流行病学调查，在此基础上，结合国外CAP诊治方面的最新研究进展，对1999年制定的《社区获得性肺炎诊断和治疗指南(草案))进行了适当修改，旨在指导临床建立可靠的诊断，全面评估病情，确定处理方针，改善预后，尽量避免不恰当的经验性治疗，减少抗生素选择的压力，延缓耐药，节约医药卫生资源。 一、CAP的临床诊断依据 1.新近出现的咳嗽、咳痰或原有呼吸道疾病症状加重，并出现脓性痰，伴或不伴胸痛。 2.发热。 3.肺实变体征和(或)闻及湿性啰音。 4.WBC>10×109/L或<4×109/L，伴或不伴细胞核左移。 5.胸部X线检查显示片状、斑片状浸润性阴影或间质性改变，伴或不伴胸腔积液。 以上1～4项中任何1项加第5项，并除外肺结核、肺部肿瘤、非感染性肺间质性疾病、肺水肿、肺不张、肺栓塞、肺嗜酸性粒细胞浸润症及肺血管炎等后，可建立临床诊断。 二、CAP的病原学诊断 1.病原体检测标本和方法：见表1。 2.痰细菌学检查标本的采集、送检和实验室处理：痰是最方便且无创伤性的病原学诊断标本，但痰易被口咽部细菌污染。因此痰标本质量的好坏、送检及时与否、实验室质控如何将直接影响细菌的分离率和结果解释，必须加以规范：(1)采集：尽量在抗生素治疗前采集标本。嘱患者先行漱口，并指导或辅助其深咳嗽，留取脓性痰送检。无痰患者检查分枝杆菌和肺孢子菌可用高渗盐水雾化吸人导痰。真菌和分枝杆菌检查应收集3次清晨痰标本；对于通常细菌，要先将标本进行细胞
2020版美国痛风指南解读 2020年5月，最新版《美国风湿病学会痛风管理指南》因推荐内容变化较大，一经发布引发了广泛热议。医脉通内分泌科于第一时间对指南的推荐部分进行了编译分享，很多老师留言发表了自己的看法。本文中，余金泉老师对指南中的几个重要推荐变化进行了解读，小编进行了整理与各位老师分享，供大家参考。 2019年11月，美国风湿病学会（ACR）学术年会上发布了2020版ACR 痛风临床实践指南（草案），笔者也在第一时间撰文进行了分享，2020年5月，2020版ACR指南正式在Arthritis Care & Research刊发，目前已有不少分享。 前面看到了不少对新指南的解读，同样有不少同行认为有翻天覆地的变化，实则不然。新版指南或许有些做法与过往推荐有了修订，但实在谈不上“翻天覆地”，而且不少推荐，笔者窃以为更重要的不是知其然，而是知其所以然——重要的不是指南怎么推荐，而是搞清楚指南推荐背后
的逻辑，这样临床上决策时才游刃有余，以及可以做出最符合患者利益的治疗。 1 痛风降尿酸治疗的指征 以下三点为中高证据强推荐的指征（板上钉钉没错了！）： ?≥1处皮下痛风石； ?有证据表明存在痛风引起的影像学破坏； ?频繁发作（≥2次/年）的痛风。 中等证据弱推荐： 以往曾发作一次以上痛风，但属于非频繁发作（＜2次/年）。 而对于首次发作的痛风患者，除了以下三种情况弱推荐应考虑降尿酸治疗：慢性肾脏病CKD3期以上；血尿酸≥9mg/dL（540μmol/L）；存在泌尿系结石。不符合以上三种情况的首次发作患者，应该谨慎推荐开始降尿酸治疗。 笔者注解1： 中国指南推荐无症状高尿酸血症降尿酸治疗的指征为：血尿酸水平≥540μmol/L或≥480μmol/L，且有下列合并症之一：高血压、脂代谢异常、
. 临床诊疗指南及药物临床应用指南 1、社区获得性肺炎的诊断及治疗 2、扁桃体炎治疗指南 3、成人水痘的症状和治疗 4、急性阑尾炎诊疗规范 5、流行性腮腺炎诊断标准 6、带状疱疹治疗指南 7、丹毒诊治指南 8、皮肤感染指南 9、上消化道出血 10、抗菌药物的合理应用 11、激素的使用
社区获得性肺炎诊断和治疗指南 中华医学会呼吸病学分会 社区获得性肺炎(community-acquired pneumonia,CAP)是指在医院外罹患的感染性肺实质(含肺泡壁，即广义上的肺间质)炎症，包括具有明确潜伏期的病原体感染而在入院后潜伏期内发病的肺炎。CAP是威胁人类健康的常见感染性疾病之一，其致病原的组成和耐药特性在不同国家、不同地区之间存在着明显差异，而且随着时间的推移而不断变迁。近年来，由于社会人口的老龄化、免疫损害宿主增加、病原体变迁和抗生素耐药率上升等原因，CAP的诊治面临许多新问题。最近，中华医学会呼吸病学分会完成了两项较大样本的全国性CAP流行病学调查，在此基础上，结合国外CAP诊治方面的最新研究进展，对1999年制定的《社区获得性肺炎诊断和治疗指南(草案))进行了适当修改，旨在指导临床建立可靠的诊断，全面评估病情，确定处理方针，改善预后，尽量避免不恰当的经验性治疗，减少抗生素选择的压力，延缓耐药，节约医药卫生资源。 一、CAP的临床诊断依据 1.新近出现的咳嗽、咳痰或原有呼吸道疾病症状加重，并出现脓性痰，伴或不伴胸痛。 2.发热。 3.肺实变体征和(或)闻及湿性啰音。 4.WBC>10×109/L或<4×109/L，伴或不伴细胞核左移。 5.胸部X线检查显示片状、斑片状浸润性阴影或间质性改变，伴或不伴胸腔积液。 以上1～4项中任何1项加第5项，并除外肺结核、肺部肿瘤、非感染性肺间质性疾病、肺水肿、肺不张、肺栓塞、肺嗜酸性粒细胞浸润症及肺血管炎等后，可建立临床诊断。 二、CAP的病原学诊断 1.病原体检测标本和方法：见表1。 2.痰细菌学检查标本的采集、送检和实验室处理：痰是最方便且无创伤性的病原学诊断标本，但痰易被口咽部细菌污染。因此痰标本质量的好坏、送检及时与否、实验室质控如何将直接影响细菌的分离率和结果解释，必须加以规范：(1)采集：尽量在抗生素治疗前采集标本。嘱患者先行漱口，并指导或辅助其深咳嗽，留取脓性痰送检。无痰患者检查分枝杆菌和肺孢子菌可用高渗盐水雾化吸人导痰。真菌和分枝杆菌检查应收集3次清晨痰标本；对于通常细菌，要先将标本进行细胞学筛选。对于厌氧菌、肺孢子菌，采用支气管肺泡灌洗液(BALF)标本进行检查的
《中国慢乙肝防治指南》2015版更新要点 医脉通？2015-10-26 ?? 2015年10月24-25日，中华医学会第十七次全国病毒性肝炎及肝病学术会议暨2015 年中华医学会感染病学分会年会、中华医学会肝病学分会年会在北京国家会议中心隆重召开。大会以“快速发展中的肝脏病学”为主题，围绕目前肝病学研究的进展及热点问题进行了专题研讨，全方位展现了肝病学领域的最新成就和发展趋势。作为本次大会最大的亮点，25日下午举行的指南发布会，正式推出了2015年版《中国慢性乙型肝炎防治指南》和《丙 型肝炎防治指南》，其中关于2015年版《中国慢性乙型肝炎防治指南》的更新要点如下： 流行病学和预防 推荐意见1:对HBsAg阳性母亲的新生儿，应在出生后24h内尽早（最好在出生后12h 内）注射HBIG剂量应》100 IU,同时在不同部位接种10卩g重组酵母乙型肝炎疫苗，在1 个月和6个月时分别接种第2和第3针乙型肝炎疫苗，可显着提高阻断母婴传播的效果（A1） 推荐意见2 :对新生儿时期未接种乙型肝炎疫苗的儿童应进行补种，剂量为10卩g重组酵母或20卩g CHO重组乙型肝炎疫苗（A1）
推荐意见3:新生儿在出生12h内注射HBIG和乙型肝炎疫苗后，可接受HBsAg阳性母 亲的哺乳（B1） 推荐意见4:对免疫功能低下或无应答者，应增加疫苗的接种剂量（如60卩g）和针次；对3针免疫程序无应答者可再接种1针60卩g或3针20卩g重组酵母乙型肝炎疫苗，并于第2次接种乙型肝炎疫苗后1-2个月检测血清中抗-HBs，如仍无应答，可再接种1针60卩g重组酵母乙型肝炎疫苗（A1）。 抗病毒治疗推荐意见 HBeAg阳性CHB患者 药物选择: 推荐意见5:对初治患者优先推荐选用ETV TDF或PeglFN （A1）。对于已经开始服用 LAM LdT或ADV治疗的患者，如果治疗24周后病毒定量＞300copies/ml，改用TDF或加用ADV治疗（A1）。 推荐疗程: 推荐意见6: NAs的总疗程建议至少4年，在达到HBV DNA氐于检测下限、ALT复常、 HBeAg血清学转换后，再巩固治疗至少3年（每隔6个月复查1次）仍保持不变者，可考虑 停药，但延长疗程可减少复发（B1）。 推荐意见7: IFN- a和PeglFN- a的推荐疗程为1年，若经过24周治疗HBsAg定量
2020骨髓瘤最新诊疗进展：复发难治多发性骨髓瘤的治疗策略 （完整版） 2020年10月30~11月1日，“2020骨髓瘤最新诊疗进展论坛（成都）”顺利召开。大会邀请我国60多位骨髓瘤相关领域的专家学者齐聚会场，围绕国内外骨髓瘤最新研究进展进行研讨。会上，上海交通大学医学院附属瑞金医院糜坚青教授以“复发难治多发性骨髓瘤的治疗策略”为题进行了分享，医脉通汇总其精华，分享如下。 NO.1多发性骨髓瘤的治疗现状 多发性骨髓瘤（MM）目前已成为第二大血液恶性肿瘤。随着我们对疾病的了解逐渐加深、早期诊断的实现以及体检的普及，目前骨髓瘤的确诊人数比以往更多，确诊患者的年龄也比以往更年轻。 目前，骨髓瘤仍不可治愈，糜教授表示，随着新药出现，患者的生存期也得到了明显的改善。80年代，骨髓瘤患者的中位总生存期（OS）仅有2年，经过30多年科学技术的发展，对于低危的骨髓瘤患者而言，中位OS可达8-10年。 尽管在过去的几十年中，骨髓瘤患者已经获得了明显的生存获益，但大多数患者最终都会复发。而且，随着复发次数的增多，复发间隙会
越来越短，预后也会越来越差，恶性程度也将越来越高（图1）。数据显示，由于患者的脱落，大约15%-35%的患者无法进入下一线治疗。因此，值得我们思考的是，如何在一线更好的治疗患者，如何在二线、三线尽量延长患者的生命。 图1 根据疾病生物学特性，骨髓瘤复发分为生化复发和临床复发。一项临床研究（图2）将252例首次复发的骨髓瘤患者分为三组：生化复发组、无髓外病变的临床复发组和有髓外病变的临床复发组。结果显示，生化复发组的OS和无进展生存期（PFS）明显优于临床复发组。另一项临床研究显示（图3），研究人员将207例骨髓瘤患者纳入分析，评估比较生化复发和临床复发的骨髓瘤患者在首次复发时接受来那度胺/地塞米松治疗的临床结局，结果表明，生化复发即进行治疗的患者可降低37%的疾病进展风险。
中国急性缺血性脑卒中诊治指南2010 急性期诊断与治疗 一、评估和诊断 (一)病史和体征 1．病史采集：询问症状出现的时问最为重要。 2．一般体格榆查与神经系统体榆：评估气道、呼吸和循环功能后，立即进行一般体格检查和神经系统体检。 3．可用脑卒中量表评估病情严重程度。常用量表有： (1)中国脑卒中患者临床神经功能缺损程度评分量表。 (2)美国国立卫生院脑卒中量表(National Institutes of}tcalth Strok|(NIHss)是目前国际上最常用量表。 (3)斯堪的纳维亚脑卒中量表(ScandinavianStmke Seale，SSS)。 (二)脑病变与血管病变检查 脑部病变检查：1 平扫CT，疑似脑卒中首选检查；2 多模式CT；3 标准MRI；4多模式MRI。 血管检查：1 颈动脉双功超声；2 TCD；3 MRA、CTA、DSA （三）实验室及影像检查选择 所有患者都应做的检查：①平扫脑cT或MRl；②血糖、肝肾功能和电解质；③心电图和心肌缺血标志物；④全血计数，包括血小板计数；⑤凝血酶原时问(Frr)、国际标准化比率(INR)和活化部分凝血活酶时问(AHT)；⑥氧饱和度； ⑦胸部x线检查。 部分患者必要时可选择的检查：①毒理学筛查；②血液酒精水平；③妊娠试
验；④动脉血气分析(若怀疑缺氧)；⑤腰穿(怀疑蛛网膜下腔出血而cT末显示或怀疑脑卒中继发于感染性疾病)；⑥脑电图(怀疑癫痫发作)。 （四）急性缺血性脑卒中的诊断可根据： (1)急性起病； (2)局灶件神经功能缺损，少数为全面神经功能缺损； (3)症状和体征持续24 h以上（溶栓可参照适应证选择患者）； (4)排除非血管性脑部病变； (5)脑CT或MRI排除脑出血和其他病变，有责任缺血病灶。 （五）急性缺血性脑卒中诊断流程应包括如下5个步骤 (1)是否为脑卒中，排除非血管性疾病。 (2)是否为缺血性脑卒中，进行脑CT或MRI检查排除出血性脑卒中。 (3)脑卒中严重程度，根据神经功能缺损量表评估。 (4)能否进行溶栓治疗，核对适应证和禁忌证（见溶栓中相关内容）。 (5)病因分型参考TOAST标准，结合病史、实验窜、脑病变和血管病变等检查资料确定病因。 推荐意见：(1)对所有疑似脑卒中患者应进行头颅平扫CT或MRI检查（I 级推荐）。(2)在溶栓等治疗前，应进行头颅平扫CT检查（I级推荐）。(3)应进行上述血液学、凝血功能和生化检查（I级推荐）。(4)所有脑卒中患者应进行心电图检查（I级推荐）。(5)用神经功能缺损量表评估病情程度（Ⅱ级推荐）。(6)应进行血管病变检查（Ⅱ级推荐），但在症状出现6 h内，不过分强调此类检查。(7)根据上述规范的诊断流程进行诊断（I级推荐）。 二、一般处理
2017 GINA哮喘指南更新要点！ 2017-02-24 来源：医脉通作者：吴一龙我要投稿 GINA哮喘
收藏( 215 )评论（1人参与）视频播放S 视频播放E ppt播放S ppt播放E 调研专用qinjian add(20140610) (S) 调研专用qinjian add(20140610) (E) 2017年2月，全球哮喘防治创议（GINA）发布了哮喘更新指南，本文是更新的重点内容。 1. 哮喘慢阻肺重叠（Asthma-COPD overlap） 哮喘慢阻肺重叠（Asthma-COPD overlap）是2017 GINA和GOLD推荐的术语，用于描述具有哮喘和慢阻肺两种疾病特征的患者。这些患者常见于临床，但很少纳入临床研究中。哮喘慢阻肺重叠不是一种单一的疾病实体，是指“哮喘”和“慢阻肺”，它可能包括由不同的基础机制引起的几种不同的表型。既往的术语哮喘慢阻肺重叠综合征（asthma-COPD overlap syndrome）或ACOS不再建议使用，因为这个术语经常被用于一种单独的疾病。 2. 更新肺功能测量 肺功能测量频率 ?肺功能评估应在诊断或治疗开始时进行；控制治疗后的3~6个月后，评估个人最佳FEV1；并且此后定期（periodically） 对定期（Periodically）进行了说明： ?大多数成人：应至少每1~2年测量肺功能 ?高风险患者频率应该更高 ?儿童根据严重程度和临床过程，频率应该更高 肺功能轨迹 ?患有持续哮喘的儿童肺功能生长可能降低，一些患者在早期成人生活中可能有肺功能加速下降的风险。
非阻塞性冠状动脉疾病：诊断和治疗 2015-04-22 来源：医脉通 患者由于胸痛就诊，被送至导管室；确诊其患有冠状动脉疾病（CAD），但不足以支持诊断为阻塞性CAD。针对这些患者的传统治疗方案是治疗已经出现的各种症状。然而，通常认为这部分患者未来发生心血管事件的风险并不会比没有CAD的患者高。最近，有研究表明这种思路是错误的：患有非阻塞性CAD 的患者，未来发生心血管事件的风险要高于没有CAD的患者。 “过去，患者因胸痛就诊，虽然负荷测试异常，但血管造影可能显示正常，医生会据此告诉患者：没什么大问题，不用担心。”斯坦福医疗中心介入心脏病学主任、副教授、医学博士William F. Fearon说道，“我们发现这些患者会可能出现血管异常，但在血管造影片中看并不明显；如果进行深入的检查，特别是侵入性的负荷、血流量和其他冠状动脉循环异常情况的检测，就能够找出胸痛的确切原因，然后指导治疗策略”。尽管如此，这些检查程序还没有纳入临床指南，大部分医生在临床中也未采用。 “现在，在包括梅奥诊所在内的几个CAD研究中心，倾向于更加全面地评估冠状动脉生理机能，但是最初的进展来自欧洲心脏病学会，他们在指南中规定，对不明原因的胸痛患者，必须检测血管内皮功能。”梅奥诊所胸痛部主任、首席研究员Amir Lerman教授，在接受采访时说，“总的来说，这仍然是一个崭新的领域。” 此外，也缺少对此类患者预防和治疗最佳方案的研究。目前面对此类患者，医生必须依靠自己的临床判断。 “能够明确的是，大多数非阻塞性CAD患者，动脉粥样硬化性心血管疾病（ASCVD）的十年风险升高，且大大高于美国心脏病学会和美国心脏协会估算的人均十年风险预期。” Cedars-Sinai医学中心的C. Noel Bairey Merz教授指出。在3月的2015ACC年会中Merz指出，“根据我的临床经验，我推荐非阻塞性CAD患者使用他汀类药物和阿司匹林，如果他们有症状，则建议进行抗心绞痛和抗心肌缺血治疗。需要在非阻塞性CAD人群中，开展研究预防性疗法的作用的临床试验。” 行动的依据 第一个引发非阻塞性CAD争议的研究是女性缺血综合征评估（WISE）研究。结果表明，患有非阻塞性CAD的女性与没有CAD的女性相比，心肌梗死（MI）风险升高，而且使用常规的诊断方法容易漏诊非阻塞性CAD。 2014年发表的VA CART研究（N = 37674；22.3%患有非阻塞性CAD），也发现了相似的结果。该研究主要针对2007-2012年在退伍军人事务部卫生保健系统中接受过选择性冠状动脉造影的男性退伍军人。VA CART研究副主任、
2018版中国急性缺血性脑卒中诊治指南简要医脉通临床指南1周前 急性缺血性脑卒中（急性脑梗死）是最常见的卒中类 型，占我国脑卒中的69.6％～70.8％。《中国急性缺 血性脑卒中诊治指南2018》是对2014版指南的更新， 突出了院前处理、急诊评估与诊断流程、急性期静脉 溶栓、血管内取栓、影像学评估等方面的进展。关于 急性缺血性脑卒中的前期诊断和一般管理，新版指南 主要有以下推荐。 推荐意见： （1）建议卫生主管部门组建区域脑卒中分级救治系统，医疗机构具备分级开展脑卒中适宜诊治技术的能力，并逐步建立认证、考核和质量改进体系（Ⅰ级推荐，C级证据）。 （2）推荐急救转运系统与医院建立有效联系及转运机制，医院建立院内脑卒中诊治绿色通道，有条件的医院逐步建立规范的远程卒中诊治系统（Ⅰ级推荐，B级证据）。 推荐意见： 对突然出现疑似脑卒中症状的患者，应进行简要评估和急救处理并尽快送往就近有条件的医院（Ⅰ级推荐，C级证据）。 推荐意见：
收治脑卒中患者的医院应尽可能建立卒中单元，所有急性缺血性脑卒中患者应尽早、尽可能收入卒中单元接受治疗（Ⅰ级推荐，A级证据）。 推荐意见： 按诊断流程对疑似脑卒中患者进行快速诊断，尽可能在到达急诊室后60 min内完成脑CT等基本评估并开始治疗，有条件应尽量缩短进院至溶栓治疗时间（DNT）（Ⅰ级推荐，B级证据）。 急性缺血性脑卒中诊断标准：（1）急性起病；（2）局灶神经功能缺损（一侧面部或肢体无力或麻木，语言障碍等），少数为全面神经功能缺损；（3）影像学出现责任病灶或症彬体征持续24 h以上；（4）排除非血管性病因；（5）脑CT/MRI排除脑出血。 诊断流程： 第一步，是否为脑卒中？排除非血管性疾病。 第二步，是否为缺血性脑卒中？进行脑CT/MRI检查排除出血性脑卒中。 第三步，卒中严重程度？采用神经功能评价量表评估神经功能缺损程度。 第四步，能否进行溶栓治疗？是否进行血管内机械取栓治疗？核对适应证和禁忌证。 第五步，结合病史、实验室、脑病变和血管病变等资料进行病因分型（多采用TOAST分型）。 推荐意见：
血管闭塞性脉管炎临床诊疗指南 【概述】 血管闭塞性脉管炎是一种累及全身中、小动脉的炎症，病理为慢性进行性血管闭塞病变。早期动脉壁增厚，管壁小血栓形成，血流受阻；晚期纤维组织增生，血管硬化，管腔闭塞。发病与吸烟、寒冷、感染、营养不良、遗传因素等有关。康复治疗目的在于解除血管痉挛，改善血液循环，减轻或消除症状。 【诊断要点】 症状多见于有吸烟嗜好的男性青壮年，下肢远端（腯动脉及以下动脉）有凉、麻、酸痛缺血性症状，继之出现间歇性跛行，重者静息痛，夜间痛。 体征肢端皮肤苍白或紫红色，局部皮肤温度低，足背动脉和胫后动脉搏动减弱或消失，重者足趾溃疡、坏死。肢体位置检查（Buergei?试验）阳性（患者平卧，下肢抬高45°，3min后观察皮肤颜色，如足部皮肤苍白、自觉麻木或疼痛者为阳性）。 肢体血流图检查可见波型呈水纹波，波幅明显降低。
超声多普勒检查显示动脉狭窄或阻塞。 【康复评定】 按临床肢体缺血程度，可分为三期。 第一期局部缺血期：患肢麻木、发凉、畏寒、不适，轻度间歇性跛行， 气温低时明显。足背或胫后动脉搏动减弱或消失，趾跖面皮色正常或稍白，但压迫试验阳性。 第二期营养障碍期：上述症状加重，末梢皮肤苍白明显，间歇性跛行明显，疼痛转为持续性静息痛，夜间更剧烈。患肢皮温降低，足背或胫后动脉搏动消失。压迫或Buerger试验强阳性。 第三期组织坏死期：组织坏疽常从足趾开始，患侧趾（指）端发黑、干瘪、坏疽、溃疡形成，合并感染可出现全身症状。小面积坏疽如无感染，多为干性坏疽；大面积的深层坏疽和（或）有感染，多为湿性坏疽。 【康复治疗】 一般治疗戒烟、防止受凉、受潮和外伤。但也要注意避免局部过热，以免增加组织需氧量，致症状加重。 物理治疗
2014年克罗恩病肛瘘分类、诊断及治疗的全球共识 (中文版) 2014-07-12 75年前，Penner而和Crohn最先描述了肛瘘为克罗恩病的并发症之一。据调查，20%的克罗恩病患者并发肛瘘，其中30%的患者会反复发作。克罗恩病诊断1年时，肛瘘的发生率为12%，当诊断时间达20年时，其发生率翻倍。 肛瘘给患者带来巨大负担，然而目前关于肛瘘的文献十分有限，为此，来自荷兰、英国、美国等多个国家的专家组成了一个工作组，搜罗了4680篇相关文献，并进行总结，得出克罗恩病肛瘘分类、诊断及治疗的全球共识，于2014年6月7日在线发表 在 Gut 杂志上。 【分类及评分】 1、一般分类和评分 （1）一套临床实用的克罗恩病肛瘘分类有助于医生选择最佳治疗方案。 推荐级别：1C。 （2）克罗恩病肛瘘活动评分必须能反应病情的严重程度及对治疗的反应。 推荐级别：1C。 讨论：目前已有好几套分类标准及评分系统来定量评价克罗恩病肛瘘的病变范围及严重程度。共识推荐最好分别制定分类标准及评分系统：制定分类标准时，应考虑解剖学因素；制定评分标准时，应评估肛瘘活动情况，并且能敏感地反应治疗效果。然而，其分类及评分都在一定程度上决定了最佳治疗方案的选择及预后。 2、肛瘘活动 肛瘘活动的评估必须同时参考临床及影像学表现（MRI）。 推荐级别：2C。 讨论：肛周疾病活动评分（PDAI）是根据患者生活质量（疼痛程度、活动及性生活受限）、肛周疾病的严重程度（瘘管流出情况、肛周疾病类型及硬化程度）制定的李克特五分量表。当PDAI>4分为界值来判定瘘管引流及局部炎症活动时，其准确性为87%。 “瘘管引流评价”最初在英夫利昔单抗相关的一项RCT研究中用来定量评估瘘管愈合情况。瘘管闭合定义为无引流（手指轻压除外）；有反应定义为连续两次随访时引流量降低
两种新型抗凝药拮抗剂前景良好 医脉通2014-01-06发表评论分享 在抗血小板药物方面，由于新型口服抗凝药（NOCA）尚无特异性拮抗剂，因此临床医生在用药上始终存在着后顾之忧。近日有充分证据显示两种NOCA拮抗剂不但可以快速逆转NOCA抗凝效应，而且不会增加血栓栓塞等并发症的风险，展现了良好发展前景。 其中一种拮抗剂Andexanet（Portola制药研发）为无生物活性的Xa因子类似物，可逆转Xa因子抑制剂（包括利伐沙班和阿哌沙班）的抗凝作用；另一种拮抗剂Fab为抗体片段（勃林格殷格翰研发），可特异性的拮抗达比加群。Andexanet和Fab的相关研究结果已分别在第55届美国血液学会(ASH)年会和2013年美国心脏协会（AHA）科学年会上公布。 瑞典Uppsala大学医学院的Lars Wallentin博士指出，对于严重出血的患者，任何新型抗凝药的拮抗剂都无能为力。他表示，目前用于出血性疾病治疗的血液制品包括新鲜冰冻血浆（FFP）、凝血酶原复合物和活化VII a因子，但关于其临床应用以及使用不当时是否增加血栓形成风险的相关资料却少之又少。 相比之下，特异性的抗凝药拮抗剂具备很多优势，通常被认为是逆转出血的最佳选择，如果患者符合相关适应证，那么用药后能够显著获益。 NOCA出血风险下降 Wallentin博士指出新型抗凝药的出血风险要低于华法林。事实上即使没有特异性的拮抗剂，也无需太过担心新型抗凝药的出血风险，但拮抗剂在实际临床工作中还是有着用武之地的，比如需要紧急行外科手术治疗的患者。 Wallentin博士对于上述拮抗剂的临床应用持支持态度，但他表示该类药物的使用频率不会太高。“我想这些NOCA拮抗剂大部分时候会被束之高阁，直到发生严重出血时才被取下用于临床，其实它更多的是为临床医生使用抗凝药提供一种心理保障；就好比在你乘机时，如果你知道机上备有降落伞，那么无疑是吃了颗定心丸。” Andexanet 相关研究数据来自健康志愿者参与的临床试验前期阶段，Wallentin博士指出下一步临床试验应纳入一定数量的出血患者，他认为对出血患者开展大规模临床试验可能有些不切合实际。相较于安慰剂对照试验，非盲法试验的可行性更大。上述试验方案的可行性正在等待
A H A心肺复苏指南发布 HEN system office room 【HEN16H-HENS2AHENS8Q8-HENH1688】
2018AHA心肺复苏指南发布，更新要点一览！ 医脉通前天 11月5日，美国心脏学会（AHA）官网及Circulation杂志刊登了三篇关于心肺复苏（CPR）和心血管急救的 指南更新文件，分别为《2018AHA心肺复苏和心血管急救指南更新：心脏骤停期间和之后立即使用抗心律失常药物进行高级心血管生命支持》、《2018AHA心肺复苏和心血管急救指南更新：儿童高级生命支持》和《2018国际复苏联合会（ILCOR）心肺复苏和心血管急救治疗推荐要点》。 2017年发布的三个文件主要更新了基础生命支持和CPR，今年的三个新文件主要关注高级生命支持和抗心律 失常药物的使用。 2018 ILCOR心肺复苏和心血管急救治疗推荐要点 成人室颤（VF）或无脉性室速（pVT）心脏骤停患者在复苏期间或自主循环恢复（ROSC）后立即使用抗心律失常药物的建议： 合并难治性休克的VF/pVT成人，建议使用胺碘酮或利多卡因（弱推荐，低质量证据）； 合并难治性休克的VF/pVT成人，不建议常规使用镁剂（弱推荐，极低质量证据）； 合并难治性休克的VF/pVT心脏骤停成人，目前证据水平太低不足以支持溴苄胺、尼非卡兰或索他洛尔的使 用； VF/pVT心脏骤停成人，目前证据水平太低不足以支持在ROSC后立即使用预防性的抗心律失常药物。 婴儿和儿童VF/pVT心脏骤停患者的抗心律失常药物使用建议： 合并难治性休克的VF/pVT儿童，建议使用胺碘酮或利多卡因（弱推荐，极低质量证据）。 2018AHA指南更新：高级心血管生命支持中抗心律失常药物的应用 成人VF/pVT心脏骤停患者在复苏期间使用抗心律失常药物的建议： 对除颤无反应的VF/pVT患者，可考虑使用胺碘酮或利多卡因。对于有目击者的心脏骤停，这些药物可能特别 有用，因为给药更及时（IIb，B-R）； 心脏骤停成人，不建议常规使用镁剂（III: No Benefit，C-LD）。尖端扭转型室速（与长QT间期相关的多 形性VT）可考虑使用镁剂（IIb，C-LD）。 图1 成人心脏骤停的救治流程-2018更新 图2 成人心脏骤停的循环流程-2018更新 利多卡因的推荐剂量：首次给药 mg/kg IV/IO，若需要，第二次给药 mg/kg IV/IO； 胺碘酮的推荐剂量：首次给药300 mg IV/IO，若需要，第二次给药150 mg IV/IO。 心脏骤停患者在ROSC后立即使用抗心律失常药物的建议： 缺乏足够的证据支持或反对ROSC后早期（在第一个小时内）常规使用β受体阻滞剂。 缺乏足够的证据支持或反对ROSC后早期（在第一个小时内）常规使用利多卡因。 若无禁忌证，当复发性VF/pVT的治疗可能具有挑战性的时候，可以在特定情况下（例如在EMS转运期间）考 虑预防性使用利多卡因（IIb，C-LD）。 此外，缺乏足够的证据支持或反对心脏骤停ROSC后常规启用或继续使用其他抗心律失常药物，包括胺碘酮。与2010版指南一致，新版指南仍然强调CPR和除颤是提高VF/pVT患者生存率的唯一手段。目前，尚未证明抗心律失常药物可以改善长期生存率或良好神经功能生存率，目前的治疗建议主要基于短期结果。
美国呼吸治疗协会临床实践指南——有创机械通气和无创机械通气时的气道湿化：2012 AARC Clinical Practice Guideline：Respir Care, 2012, 57(5):782–788. 译者：中日友好医院ICU 孙菁夏金根 1.有创通气患者均应进行气道湿化。 2.主动湿化可以增加无创通气患者的依从性和舒适度。 3.有创通气患者进行主动湿化时，建议湿度水平在33~44mg H2O/L之间，Y型接头处气体温度在34~41℃之间，相对湿度达100％。 4.有创通气患者进行被动湿化时，建议热湿交换器提供的吸入气湿度至少达到30mg H2O/L。 5.不主张无创通气患者进行被动湿化。 6.对于小潮气量患者，例如应用肺保护性策略时，不推荐使用热湿交换器进行气道湿化，因为这样会导致额外死腔的产生，增加通气需求及PaCO2 。 7.不建议应用热湿交换器以预防呼吸机相关性肺炎。 HMV 1.0 概述 有创通气时因上呼吸道被旁路，湿化对于预防低体温、呼吸道上皮组织的破坏、支气管痉挛、肺不张以及气道阻塞有着至关重要的作用。某些严重情况下，气道分泌物的过于黏稠可导致气管插管阻塞。然而，目前仍无明确观点表明额外的加热、加湿对于无创通气具有明确的必要性，但是湿化的确可以增加无创通气患者的舒适度。 两种湿化装置可以用于有创通气患者吸入的气体的加热湿化，主动湿化是指通过加热湿化器进行主动加温加湿，被动湿化是通过热湿交换器（人工鼻）来进行的。目前有三种类型的热湿交换器或者人工鼻：疏水型、亲水型和过滤功能型。 主动加热湿化器通过对吸入气体加温并增加水蒸气的含量来进行加温、加湿。被动加热湿化器（人工鼻）的工作原理是指通过储存患者呼出气体中的热量和水分来对吸入气体进行加热湿化。 上呼吸道可提供75%的热量和水分给肺泡。当上呼吸道不能对吸入气体进行加温湿化时，湿化器就需要补偿丢失的这部分热量和水分。比如说，总的水分需求吸
医脉通2014-08-19发表评论(1人参与)分享 获加拿大卫生部批准的焦虑治疗药物一览 流行病学 社交恐怖症（SAD）是最常见的焦虑障碍之一，终生患病率约为8-12%，女性较男性常见，发达国家发病率（6.1%）较发展中国家高（2.1%）。SAD发病较早，多起病于青春期（平均12岁），常呈慢性迁延病程。低教育成就、低社会经济地位、单身或与伴侣分离、共病重性抑郁（MDD）与SAD发病率的升高相关。
SAD常导致严重的功能损害，包括教育及职业表现、家庭功能及生活质量的总体下降。该病同样对个体及社会造成沉重的经济负担。罹患SAD的加拿大人在过去两周内报 告至少一个残疾日（disability day）的可能性是其他人的2倍。 精神科共病 SAD的精神科共病率很高，72%的SAD患者均满足另一种精神障碍的诊断标准。最常见的共病为MDD及其他焦虑相关障碍，共病回避型人格障碍、躯体变形障碍、物质使 用障碍、注意缺陷多动障碍（ADHD）及精神分裂症也较为常见。 DSM-5诊断标准 DSM-IV-TR将与其他医学状况相关或继发于其他医学状况的社交恐怖及回避行为排 除在外。然而，DSM-5认识到，SAD完全可能继发于某种医学问题，如口吃、帕金森病 导致的震颤、肥胖、烧伤或损伤所致毁容，这些个体同样可能因为社交恐怖导致功能受损。 另外，DSM-5移除了DSM-IV-TR中的“广泛型”社交恐怖症，同时添加了“仅限于表演”这一亚型。原因在于，并无足够证据支持“广泛型”的诊断，同时有证据显示，SAD的严重度随恐怖症状数量的变化而处于谱系的不同位置中。
尽管以上呈现的是最新诊断标准，但需要指出的是，以下治疗相关内容均基于满足DSM-IV诊断标准的患者。 心理治疗 认知行为治疗（CBT）是SAD非药物治疗的金标准。针对SAD的CBT认知技术包 括重构及挑战病态思维，而行为组分主要为暴露疗法。很多随机对照研究（RCTs）及meta分析均提示，CBT针对SAD的疗效优于安慰剂、常规治疗（TAU）或等候名单（wait-list）设置。尽管结果有所不同，但仍有多项研究提示，在治疗急性SAD方面，CBT与药物治疗疗效相仿。还有研究显示，在治疗中断后，CBT疗效的持续时间较药物治疗更长。针对SAD的CBT包括团体及个人形式。尽管有研究显示，个人CBT的疗效优 于团体CBT，meta分析结果则显示，两者疗效并无显著差异。 既往研究同样检视了CBT中个别组分的疗效。证据显示，单独的暴露疗法即具有一 定疗效。然而，暴露疗法与CBT整体疗效的比较结果莫衷一是。 有研究对CBT中的若干变量进行了探讨。例如证据显示，录像反馈技术并不能增强 暴露疗法的疗效。然而，两项meta分析结果显示，CBT联合个体化虚拟现实暴露疗法（VRE）效果优于等候名单对照，与纳入拟放松及现场暴露法的CBT疗效相仿。 在改善社交焦虑方面，一种聚焦于人际间行为的CBT形式与CBT疗效相仿，同时可改善关系满意度及社交亲近行为。人际疗法（IPT）针对SAD的疗效证据不一：有的研究结果为阴性，还有研究显示，IPT的疗效优于等候名单，劣于传统CBT。 与之类似，虽然疗效亦不如CBT，但正念疗法（MBT）同样可改善SAD症状。另外，针对注意偏倚训练的小规模研究显示，该疗法有助于患者脱离负性社交线索，但结果同样 存在冲突。 整合认知行为治疗（ICBT）是一种相对较新的治疗形式，或有助于提高日后针对焦 虑及心境障碍的CBT的可获得性。研究显示，ICBT在改善SAD症状方面显著优于等候 名单对照。大部分ICBT项目中，治疗师与患者的接触程度均维持在最低限度，主要形式